Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of anticonvulsant treatment upon (1) chronically increased seizure susceptibility, (2) on late increases in peptide levels and (3) on seizure-induced brain damage was investigated during various stages of acute kainic acid (10 mg/kg i.p.)-induced seizures. The seizures were interrupted at various stages of the syndrome (50 min to 24 h after injection of the toxin) by injecting thiopental (50 mg/kg i.p.) or the excitatory amino acid antagonist, MK-801 (10 mg/kg i.p.). The increase in neuropeptide Y and somatostatin levels in the frontal cortex could be prevented by early injection of either anticonvulsant (up to 180 min after kainic acid). No protection against the increase in peptide levels was observed when the anticonvulsants were applied later. Kainic acid-induced neuronal damage in the amygdala, with glutamate decarboxylase as a neurochemical marker, was entirely prevented by interrupting seizures up to 2 h after kainic acid. Partial protection (about 40-50%) was even found when the anticonvulsant treatment was applied after the acute syndrome, as late as 8 h after kainic acid injection. Chronically increased seizure susceptibility induced by kainic acid was not prevented, even by early injection (90 min after kainic acid) of the anticonvulsant drugs. The data indicate that (1) the late increase in seizure susceptibility may be initiated early after injection of kainic acid. (2) the late increase in peptide levels may be related to the frequency of acute seizures rather than to a change in seizure threshold or brain damage and (3) even late anticonvulsant therapy may antagonize seizure-induced brain damage in the amygdala.
 ...
PMID:Effect of anticonvulsant treatment on kainic acid-induced increases in peptide levels. 197 15

Hippocampal neurons containing somatostatin have been shown to be vulnerable in some experimental models of epilepsy. In this report, we describe our recent findings about the seizure-related changes in somatostatin in brain tissue and cerebrospinal fluid (CSF) in experimental and human epilepsy. These data strengthen the view that the somatostatinergic system is affected in epilepsy.
 ...
PMID:Somatostatin and epilepsy. 197 3

1. The tetradecapeptide somatostatin (SS) has a widespread, uneven distribution within several organs including the central nervous system (CNS), with particularly high concentration in the hypothalamus. 2. The SS-related peptides (SS28, SS28(1-12), SS28(15-28)) are originated from the precursor pre-prosomatostatin. 3. SS is suggested to be involved in a large number of CNS functions, locomotion, sedation, excitation, catatonia, body temperature, feeding, nociception, paradoxical sleep, self-stimulation, seizure, learning and memory. 4. SS influences central neurochemical processes. 5. It is possible that SS is related to various neurological and psychiatric illnesses, like Huntington's disease, multiple sclerosis, Parkinson's disease, epilepsy, eating disorders, Alzheimer's disease, schizophrenia and major depressive illness.
 ...
PMID:Preclinical and clinical studies with somatostatin related to the central nervous system. 197 75

As neuropeptides may play a role in the electrical kindling model of epileptogenesis, hippocampal somatostatin, Met-enkephalin and cholecystokinin were studied by immunocytochemistry in rats 24 h following full hippocampal kindling (three stage 5 seizures). As control animals we used sham-kindled rats, unoperated rats and rats subjected to a single electroshock-induced seizure. In addition, the distribution of septohippocampal, cholinergic fibers and hippocampal mossy fibers were studied by histochemistry. The important finding was that after kindling there was, as compared to unoperated control, (1) a marked increase of somatostatin immunoreactivity in cell bodies in the dentate hilus and their presumed projections area in the outer parts of the dentate molecular layer, and (2) a marked increase of Met-enkephalin immunoreactivity in hippocampal mossy fiber terminals. We found no evidence of aberrant sprouting of mossy fiber collaterals in the fascia dentata.
 ...
PMID:Increased somatostatin and enkephalin-like immunoreactivity in the rat hippocampus following hippocampal kindling. 197 72

A selective loss of somatostatin (SS)-containing neurons in the hilar region has been reported in patients suffering from temporal lobe epilepsy. Conversely, neurons containing calcium-binding proteins such as parvalbumin (PARV) are known to be very resistant under experimental seizure conditions. In this study, we analyzed the coexistence of SS and PARV in neurons of the rat fascia dentata by using serial semi-thin cryostat sections for pre-embedding immunocytochemistry. Our results show that only 5.7% of the SS-immunoreactive hilar neurons contain PARV. The data suggest that SS-containing hilar neurons are less protected against seizure-induced calcium overload than other neurons containing calcium-binding proteins.
 ...
PMID:Most somatostatin-immunoreactive neurons in the rat fascia dentata do not contain the calcium-binding protein parvalbumin. 198 Feb 25

1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactin-secreting adenomas) indications in clinical practice. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed.
 ...
PMID:Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system. 227 50

The time-dependent pro- and anticonvulsant effects of cysteamine, a depletor of somatostatin, were investigated on the development and expression of amygdaloid kindled seizures. Acute administration of cysteamine (25-400 mg/kg, i.p.) produced a dose-dependent potentiation of kindled seizures when evoked 4 h after the drug. However, the seizures initiated 1 day after drug administration were dose-dependently suppressed. Furthermore, elicitation of seizures 4 h after cysteamine enhanced its anticonvulsant effects at 1 day after the drug, causing a parallel left shift of the dose-response curve. Since it has been reported that somatostatin is released during generalized seizures, the seizures given 4 h after cysteamine may encourage the somatostatin depletion by cysteamine and thereby potentiate its later anticonvulsant effects. The repeated administration of cysteamine (100 mg/kg, i.p.) during kindling development strongly retarded the development of generalized seizures but not the development of focal seizures or of afterdischarges in the amygdala. In contrast to the acute experiments, kindling stimulation given 4 h after each cysteamine treatment did not augment the blocking effect on kindling development. These data indicate that chronic cysteamine treatment has a strong inhibitory effect on the development of amygdaloid kindling.
 ...
PMID:Time-dependent pro- and anticonvulsant effects of cysteamine on the development and expression of amygdaloid kindled seizures. 228 75

Neuropeptide Y (NPY) immunoreactivity and gene expression was investigated in the hippocampus after kainic acid-induced seizures and pentylenetetrazol kindling in the rat. Pronounced increases of NPY immunoreactivity were found in the terminal field of mossy fibers in both animal models. In kainic acid-treated rats the peptide progressively accumulated in the hilus and the stratum lucidum of CA3, 5-60 days after injection of the toxin and, at the later intervals, extended to the supragranular molecular layer of the dentate gyrus indicating sprouting of these neurons. Unilateral injection of colchicine into the hilus abolished NPY staining of the mossy fibers. Using in situ hybridization, in both animal models markedly enhanced expression of prepro-NPY mRNA was observed in the granular layer, containing the perikarya of the mossy fibers. It is suggested that sustained expression of the neuromodulatory neuropeptide NPY, in addition to the observed plastic changes, may contribute to altered excitability of hippocampal mossy fibers in epilepsy. Neither somatostatin immunoreactivity nor gene expression were enhanced in granule cells/mossy fibers.
 ...
PMID:Neuropeptide Y biosynthesis is markedly induced in mossy fibers during temporal lobe epilepsy of the rat. 235 14

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).
 ...
PMID:Acromegaly in 14 cats. 240 66

The neuropeptides somatostatin, neurotensin and substance P were investigated in rats during and after limbic seizures induced by systemic injection of kainic acid (10 mg/kg, i.p.). Three hours after injection of the toxin, pronounced decreases (40-50%) in somatostatin-like immunoreactivity in frontal cortex, striatum, dorsal hippocampus and amygdala/pyriform cortex were observed. Concomitantly, neurotensin-like and substance P-like immunoreactivities were also reduced in the frontal cortex and the hippocampus. These early decreases in peptide levels may result from increased release and subsequent inactivation of the peptides during acute seizures. At later time intervals, 3, 10 and 30 days after injection of kainic acid, the initially decreased peptide levels were partially normalized. However, the reduction in somatostatin-like immunoreactivity in amygdala/pyriform cortex and striatum persisted up to 30 days. Neurotensin-like immunoreactivity remained decreased in the frontal cortex. On the other hand, neurotensin- and substance P-like immunoreactivities were increased in the striatum and substantia nigra 10-30 days after injection of kainic acid. These late changes in peptide levels may suggest destruction of peptidergic neurons or adaptive changes induced by the convulsions. Pretreatment of rats with cysteamine (100 mg/kg, i.p.), an agent which decreases brain somatostatin levels, had no effect on the intensity of kainic acid induced convulsions, although a slightly earlier onset of seizures was observed. The changes in peptide levels, especially the marked decreases in somatostatin content after systemic injection of kainic acid, suggest considerable acute and chronic alterations in peptidergic systems caused by limbic convulsions.
 ...
PMID:Kainic acid induced seizures: changes in somatostatin, substance P and neurotensin. 242 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>