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

Early Pb exposure is known to disrupt the development of the hippocampus and result in deficits in learning and memory capacities and altered seizure susceptibility. The excitatory amino acid, NMDA, is found in high concentrations in the hippocampus and has been implicated in learning and memory functions and seizure activity. Rat pups nursed mothers exposed to high (4%), moderate (0.4%), or low (0.05%) levels of PbCO3 in their diet, or a Na2CO3 control diet from postnatal day 1 (P1) to P25. Rat pups were injected with varying doses of NMDA on P15 or P25. Control animals showed a characteristic slowly developing response to NMDA, usually including tail twitches and wet dog shakes at approximately 10 and 40 mg/kg at P15 and P25, respectively, with status epilepticus and death occurring at 40 and 80 mg/kg. Lead-exposed animals displayed an altered sensitivity to NMDA, with high and medium Pb animals showing the onset of behavioral signs and death at lower NMDA doses, the degree of which being dependent on the level of Pb exposure. Low Pb-exposed animals showed a more variable and attenuated response to NMDA. The data are discussed in terms of the possible mechanisms of Pb neurotoxicity.
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PMID:Altered sensitivity to NMDA following developmental lead exposure in rats. 140 40

Induction of the proto-oncogene c-fos is often considered to be a marker of increased neuronal activity. We have used in situ hybridization to study the pattern of c-fos expression in limbic structures following kainic acid-induced seizures during the postnatal period in the rat. Prior to postnatal day 13 (P13), seizure activity did not result in c-fos induction in any limbic structure. Between P13 and P25, a gradual increase in c-fos expression was observed in hippocampus and cortical structures. These results were corroborated by nuclear run-off transcription assay. Thus, alterations in c-fos transcription that may facilitate stimulus-transcription coupling occur during postnatal development. The possible relationship between the postnatal maturation of c-fos expression and the increase in susceptibility of specific neuronal populations to seizure-induced cell damage is discussed.
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PMID:Absence of c-fos induction in neonatal rat brain after seizures. 163 64

We measured chronic electrocorticography (ECoG) of sensorimotor cortex during contralateral median nerve stimulation in 6 patients with partial seizures evaluated for surgery. We analyzed the spatiotemporal structure of the somatosensory evoked response (SER) using multiple source modeling to investigate functional anatomy of its neuronal sources. Two dipole sources in postcentral gyrus explained the large majority of the first 60 msec of the SER, indicating a subregion of hand somatosensory cortex generating this activity. The source locations agreed with normal functional anatomy from cortical stimulations, intraoperative photographs, and postoperative neurological examinations after focal excisions. The time patterns of both sources were biphasic like the previously described N20-P30 and P25-N35 peaks. The spatiotemporal patterns of both sources overlapped. Spatiotemporal analysis with multiple dipole sources appears useful to determine the number, locations, and spatiotemporal field patterns of cortical regions active during peripheral somatosensory stimulation and reveals simplicity in the macroscopic functional anatomy of dynamic human sensorimotor cortex.
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PMID:Functional anatomy of human hand sensorimotor cortex from spatiotemporal analysis of electrocorticography. 170 16

1. To clarify the generators of human short-latency somatosensory evoked potentials (SEPs) thought to arise in sensorimotor cortex, we studied the effects on SEPs of surgical excision of somatosensory or motor cortex in humans and monkeys. 2. Normal median nerve SEPs (P20-N30, N20-P30, and P25-N35) were recorded from the cortical surface of a patient (G13) undergoing a cortical excision for relief of focal seizures. All SEPs were abolished both acutely and chronically after excision of the hand area of somatosensory cortex. Similarly, excision of the hand area of somatosensory cortex abolished corresponding SEPs (P10-N20, N10-P20, and P12-N25) in monkeys. Excision of the crown of monkey somatosensory cortex abolished P12-N25 while leaving P10-N20 and N10-P20 relatively unaffected. 3. After excision of the hand area of motor cortex, all SEPs were present when recorded from the cortical surface of a patient (W1) undergoing a cortical excision for relief of focal seizures. Similarly, all SEPs were present in monkeys after excision of the hand area of motor cortex. 4. Although all SEPs were present after excision of motor cortex in monkeys, variable changes were observed in SEPs after the excisions. However, these changes were not larger than the changes observed after excision of parietal cortex posterior to somatosensory cortex. We concluded that the changes were not specific to motor cortex excision. 5. These results support two major conclusions. 1) Median nerve SEPs recorded from sensorimotor cortex are produced by generators in two adjacent regions of somatosensory cortex: a tangentially oriented generator in area 3b, which produces P20-N30 (human) and P10-N20 (monkey) [recorded anterior to the central sulcus (CS)] and N20-P30 (human) and N10-P20 (monkey) posterior to the CS; and a radially oriented generator in area 1, which produces P25-N35 (human) and P12-N25 (monkey) recorded from the postcentral gyrus near the CS. 2) Motor cortex makes little or no contribution to these potentials.
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PMID:Cortical somatosensory evoked potentials. II. Effects of excision of somatosensory or motor cortex in humans and monkeys. 191 77

Pathologically enhanced somatosensory evoked potentials (giant SEPs) were recorded in 10 patients with cortical myoclonus of various origins. With non-cephalic reference electrodes a giant frontal negativity corresponding to normal N30 was found over the contra- and ipsilateral hemispheres which was not simply a phase reversal of the well-known enhanced parietal P25. The preceding far-field P14, parietal N20 and frontal P22 were of normal size. A similar result was found when SEPs were studied during the action of etomidate, an ultrashort-acting non-barbiturate hypnotic which produced a marked increase of the parietal P25 and frontal N30 after intravenous administration. These increased components, on the other hand, were abolished when recording was repeated immediately after application of electroconvulsive shock whereas P14, N20, and P22 remained more or less unchanged in both conditions. Our results indicate that there are neuronal elements in the sensorimotor cortex which are more resistant to influences such as narcotic drugs and seizure activity than others, being highly modifiable by these alterations. It is speculated whether these highly modifiable cortical systems are those in which giant SEPs, as well as pharmacologically increased SEP components, arise.
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PMID:Frontal and parietal components of enhanced somatosensory evoked potentials: a comparison between pathological and pharmacologically induced conditions. 245 99

The amplitude of flash visual evoked potential (F-VEP) and somatosensory evoked potential (SEP) was found to be initially slightly higher in two untreated patients with juvenile myoclonic epilepsy (JME). Patients were studied before and after complete control of seizures with valproate. In both patients valproate prolonged the latencies of the waves IV and V and lowered the amplitudes of waves V and VI of the F-VEP. The N20-P25 amplitude in SEP in both parties was also lowered by valproate. These results may suggest that slightly higher cortical excitability in untreated JME was controlled by valproate.
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PMID:Valproate lowered the amplitude of visual and somatosensory evoked potentials in two cases of untreated juvenile myoclonic epilepsy. 947 31

Prolonged seizures in the adult brain causes neuronal loss in the hippocampus and aberrant growth (sprouting) of granule cell axons (mossy fibers) in the supragranular zone of the fascia dentata and stratum infrapyramidale of CA3. There is considerable evidence that these changes in neuronal growth following seizures are age related, with younger animals having fewer reactive changes following prolonged seizures than older animals. However, there is little information available regarding the age at which seizures in the developing brain result in alterations in axonal growth and synapse formation. In this study, we evaluated the effects of kainic acid (KA)-induced seizures during development on synaptic reorganization using the expression of growth-associated protein-43 (GAP-43), a marker for synaptogenesis and Timm stain which detects the presence of zinc in granule cell axons. Age specific doses of KA were used to induce seizures of similar intensity at various ages (postnatal days (P) 12, 21, 25, 35, 45, 60) in Sprague-Dawley rats. Up to the age of P25, there were no differences in either Timm or GAP-43 staining between animals with KA seizures and controls. In P25 and older KA-treated rats, Timm staining was found in the supragranular layer of the dentate gyrus. This staining increased with age at the time of KA injection. Seizures in adult (P60), but not younger rats also resulted in increased staining in the suprapyramidal layer of the CA3 subfields. Changes in GAP-43 were delayed compared to the Timm staining with no differences between KA-treated animals and controls until P35 when a band of GAP-43 immunostaining appeared in the supragranular inner molecular layer, progressively increasing in intensity and thickness with time. This study demonstrates that seizure-induced reactive synaptogenesis is age-related. Since both Timm and GAP-43 reflect different aspects of reactive synaptogenesis, used in combination these methods provide useful information about the structural changes following seizures during development.
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PMID:Synaptic reorganization following kainic acid-induced seizures during development. 959 78

To assess long-term metabolic consequences of recurrent ictal events arising during development, seizures were repeatedly generated in rats at different stages of cerebral maturation. Seizures were induced by i.p. injections of bicuculline for three consecutive days, starting from postnatal day 5 (P5), when the brain is very immature, or from P15, a period at which the brain is more structurally organized. Local cerebral metabolic rates for glucose were measured in 74 structures at P15, P25 and in adults (P60), by the autoradiographic method using 2-D-[14C]deoxyglucose. Repeated seizures in P5 to P7 pups led to a reduction (16-34%) of glucose consumption at P15, mainly significant in sensory, motor and functionally non-specific areas as well as in cerebellar nuclei. Selective decreases in metabolic activity were still recorded in adults, mostly in auditory system (20%) and cerebellar nuclei (27%). Seizures generated from P15 to P17 led to an overall mortality rate of 62% (versus 22% at P5 to P7). Surviving animals exhibited reduced metabolic rates for glucose (by 7-27%) at P25, significant in 23 structures, and depicting pronounced changes in limbic, hypothalamic, sensory and white matter areas, whereas brain functional activity finally returned to basal values at P60. Therefore, while younger rats seemed to better tolerate repeated bicuculline-induced seizures than older animals, the reverse was true for long-term metabolic effects, and the more immature the brain when seizures arise, the more persistent the functional consequences.
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PMID:Medium- and long-term effects of repeated bicuculline-induced seizures in developing rats on local cerebral energy metabolism. 968 3

In some children, epilepsy is a catastrophic condition, leading to significant intellectual and behavioral impairment, but little is known about the consequences of recurrent seizures during development. In the present study, we evaluated the effects of 15 daily pentylenetetrazol-induced convulsions in immature rats beginning at postnatal day (P) 1, 10, or 60. In addition, we subjected another group of P10 rats to twice daily seizures for 15 days. Both supragranular and terminal sprouting in the CA3 hippocampal subfield was assessed in Timm-stained sections by using a rating scale and density measurements. Prominent sprouting was seen in the CA3 stratum pyramidale layer in all rats having 15 daily seizures, regardless of the age when seizures began. Based on Timm staining in control P10, P20, and P30 rats, the terminal sprouting in CA3 appears to be new growth of axons and synapses as opposed to a failure of normal regression of synapses. In addition to CA3 terminal sprouting, rats having twice daily seizures had sprouting noted in the dentate supragranular layer, predominately in the inferior blade of the dentate, and had a decreased seizure threshold when compared with controls. Cell counting of dentate granule cells, CA3, CA1, and hilar neurons, with unbiased stereological methods demonstrated no differences from controls in rats with daily seizures beginning at P1 or P10, whereas adult rats with daily seizures had a significant decrease in CA1 neurons. Rats that received twice daily seizures on P10-P25 had an increase in dentate granule cells. This study demonstrates that, like the mature brain, immature animals have neuronal reorganization after recurrent seizures, with mossy fiber sprouting in both the CA3 subfield and supragranular region. In the immature brain, repetitive seizures also result in granule cell neurogenesis without loss of principal neurons. Although the relationship between these morphological changes after seizures during development and subsequent cognitive impairment is not yet clear, our findings indicate that during development recurrent seizures can result in significant alterations in cell number and axonal growth.
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PMID:Mossy fiber sprouting after recurrent seizures during early development in rats. 998 96

In order to assess long-lasting consequences of recurrent seizures during development, the effects of repeated seizures in developing rats were investigated on brain adenosine A1 and A2A receptors. The characteristics of A1 and A2A receptors were analyzed by measuring the binding of the selective agonists [3H]CHA (N6-cyclohexyladenosine) and [3H]CGS 21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine), respectively, on cerebral membrane preparations, whereas receptor coupling to G-proteins was examined by using a GTP analogue (Gpp(NH)p; guanylyl-5'-imidodiphosphate). Seizures were induced by bicuculline once a day at two different developmental stages: either from postnatal day 5 to postnatal day 7 (P5-P7) or from P15 to P17. Adenosine receptors were then studied at P15, P25 and P60. P5-P7 seizures led to an increase in A1 receptor density at P60 and to a decrease in their coupling to G-proteins at P15, but they did not affect A2A receptors. P15-P17 seizures decreased the coupling of A1 receptors to G-proteins at P25 and P60, reduced the density of A2A receptors at P25 and increased their affinity at P60. These results depict a persistent sensitivity of both A1 and A2A brain adenosine receptors to repeated seizures, with selective receptor alterations according to the cerebral maturational stage when seizures occur. In respect to the neuromodulatory and anticonvulsant properties of adenosine, such changes might be implicated in long-term functional brain reorganization after early seizures and future susceptibility to convulsive disorders.
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PMID:Medium- and long-term alterations of brain A1 and A2A adenosine receptor characteristics following repeated seizures in developing rats. 1041 17


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