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N Mikuni

Publications and source records attributed to N Mikuni.

At least 19 recordsLinked to original sources
PubMed2003

Seizures arising from the inferior parietal lobule can show ictal semiology of the second sensory seizure (SII seizure).

A 52-year-old right handed man presented with medically intractable partial seizures consisting of numbness on the left upper back spreading to the left upper as well as lower limbs. Head computed tomography and magnetic resonance imaging showed a round calcified lesion in the depth of the superior ramus of the right sylvian fissure. Ictal electrocorticographic recording with chronically implanted subdural electrodes showed low voltage fast activities starting exclusively from an electrode located on the right inferior parietal lobule. No apparent ictal activities were observed from the depth electrodes inserted in the parietal operculum. Somatosensory evoked potentials of 75 ms to 145 ms latency were recorded from the ictal onset zone, which was 2 cm caudal to the perisylvian area corresponding to the second somatosensory area. Seizures arising from the inferior parietal lobule including the angular and supuramarginal gyri can produce partial seizures whose ictal semiology and scalp electroencephalography are indistinguishable from the ones originating from the second somatosensory area.

Evoked Potentials, Somatosensory↗
PubMed2000

NMDAR1 receptor proteins and mossy fibers in the fascia dentata during rat kainate hippocampal epileptogenesis.

We examined the time course of NMDAR1 (NR1) immunoreactivity (IR) in the rat inner molecular layer of the dentate gyrus following unilateral intrahippocampal (hilar) kainic acid (KA) lesions and compared them to progressive aberrant mossy fiber (MF) sprouting into the inner molecular layer (IML). The results demonstrated that NR1 receptors in the IML of the KA side were decreased as early as 3 days after KA-induced denervation, then significantly increased at postinjection day (PID) 7. The densities of NR1 IR in the IML continued to increase up to 5 months. By comparison, MF sprouting did not occur significantly in the IML until PID 17, 10 days after NR1 IR was significantly increased. Recurrent MF-IML neoinnervation significantly increased on days 17, 60, and 150. This progressive MF innervation was significantly correlated with NR1 increases. These results suggest that NR1 receptors were decreased soon after KA-induced deafferentation of granule cell dendrites in the IML; however, they were replaced by new NR1 receptors at increased densities in the granule cell dendrites, which may have released neurotrophic factors to stimulate growth cones of MFs to reinnervate the IML. The progressive increases of NR1 and MFs in the IML suggest that such neosynaptogenesis would contribute monosynaptic recurrent excitatory mechanisms for focal hippocampal hyperexcitability and seizure onsets.

Animals↗
PubMed2000

Increase of intestinal calcium absorption and bone mineral density by heated algal ingredient (HAI) in rats.

Active absorbable calcium (AAACa) produced by adding HAI (heated algal ingredient) to oyster shell calcium (AACa) is quite efficiently absorbed from the intestine and can increase bone mineral density in elderly osteoporotic patients. HAI was produced by heating the seaweed Cystophyllum fusiforme under reduced pressure, extracting with 6N HCL, and partially neutralizing it. Butanol-ethanol extraction then yielded active HAI fraction A, corresponding to about 1% in weight. The active HAI fraction increased intestinal Ca absorption as shown by a dose-dependent increase of plasma Ca in young male parathyroidectomized rats maintained on a low-Ca diet by administration through a stomach tube with a constant dose of AACa. The action of the active fraction A to maintain bone mass was then tested in young male rats kept on a low-Ca diet for 2 weeks. Bone weight, trabecular bone density, and strength-strain index as indices of bone strength measured by peripheral computed tomography (pQCT) tended to increase when the active HAI fraction was given along with Ca. HAI increased intestinal Ca absorption and prevented the decrease of bone density in rats kept on a low-Ca diet.

Animals↗
PubMed2000

Use of cavernous sinus EEG in the detection of seizure onset and spread in mesial temporal lobe epilepsy.

PURPOSE: The study goal was to evaluate the clinical usefulness of intravenous EEG recording by placing wire electrodes in the cavernous sinus (CS) and the superior petrosal sinus (SPS) in patients with intractable temporal lobe epilepsy (TLE), with special emphasis on the ictal recording. METHODS: We placed Seeker Lite-10 guide wire as electrodes in the bilateral CS, SPS, or both to simultaneously record both ictal and interictal EEGs with the scalp EEG in five patients with TLE. In addition, in one patient, we averaged interictal scalp and intravascular EEG time-locked to the epileptiform discharge recorded from the CS/SPS-EEG to further delineate the relationship of the spikes between scalp and intravenous recording. RESULTS: In four of five patients, clinically useful recording was obtained to determine ictal focus. We recorded habitual seizures in three patients, and the detailed characteristics of ictal epileptiform discharges were shown. The averaged waveform of interictal epileptiform discharges clarified the spike distribution in the scalp EEGs, which was otherwise undetectable in the single trace. All of the patients completed the intravenous EEG monitoring without any neurological or psychological problems. CONCLUSIONS: The CS/SPS-EEG is a relatively noninvasive method that is useful for the detection of ictal focus and its spreading pattern and thus for the selection of surgical candidate among patients with intractable TLE. Although the number of seizures detected during the short monitoring period may be limited, due to the advantages of its safety and simplicity, it is worth trying for potential surgical candidates before more invasive examinations are applied. A further study with a larger number of patients is needed to estimate its practical risk.

Adult↗
PubMed2000

Brain plasticity and cellular mechanisms of epileptogenesis in human and experimental cortical dysplasia.

PURPOSE: The cellular mechanisms that may contribute to epilepsy in resected human cortical dysplasia (CD) were compared with the in utero radiated rat CD model. In human and rat focal hippocampal epilepsy, postsynaptic N-methyl-D-aspartate receptors are up-regulated and presynaptic axon collaterals hyperinnervate them. We hypothesized that in both human and rat CD: (a) the N-methyl-D-aspartate receptor subunits NR1 and NR2A/B would be increased and coassembled, and (b) aberrant axons would be in regions of CD. METHODS: Tests for presynaptic and postsynaptic changes in human and rat CD included the following: (a) cytology, (b) immunocytochemistry, (c) coimmunoprecipitation, (d) double-labeled immunofluorescence, and (e) Timm histochemistry of hippocampal mossy fibers. Within-patient comparisons were made between epileptic tissue, identified by subdural electro-encephalographic seizure onsets, and nonepileptic tissue remote from the focus but within the therapeutic resection. Rats were radiated at embryonic day 17, and offspring were studied postnatally. Statistical comparisons were made against normal rats matched for age and tissue processing. RESULTS: In focal CD patients, NR2A/B subunits and their coassemblies with NR1 were increased significantly more than for the remote nonepileptic cortex. Confocal microscopy showed that NR1-NR2A/B colabeled single dysplastic neurons in both human and rat. In CD rats, mossy fibers innervated the anomalously oriented hippocampal neurons. CONCLUSIONS: Human epileptic CD exhibits a spectrum of abnormal cell orientations and laminations that must require plastic axodendritic changes during development. These altered circuits and receptors could account for the seizures and cognitive deficits found in patients with CD. The radiated rat CD model with cortical dyslaminations and NR2A/B subunit increases would allow the development and testing of drugs targeted at only the NR2A/B subunit or at decoupling the NR1-NR2 coassembly, which could provide a specific antiepileptic drug for dysplastic circuits without inducing general depression of all brain neurons.

Abnormalities, Radiation-Induced↗
PubMed1999

Increased NR1-NR2A/B coassembly as a mechanism for rat chronic hippocampal epilepsy.

The N-methyl-D-aspartate receptors (NMDAR) produce physiologically functional channels for enhanced excitatory neurotransmission when they exist as heteromeric complexes containing the NMDAR1 subunit combined with NMDAR2. We examined the expressions of NMDAR1 and 2A/B protein in the kainic acid induced rat chronic epileptic hippocampus. Immunoreactivities of both NMDAR1 and NDMAR2A/B were increased in the inner molecular layer of the dentate gyrus, while they were decreased in the hilar and CA3/4 pyramidal zones. Immunoblot analysis demonstrated that the overall level of NMDAR1-2A/B coassembly was increased in the whole hippocampus. These results indicate that the increase of the NMDAR1-2A/B complex in the inner molecular layer is a significant cellular mechanism that contributes to focal hyperexcitability in rat chronic hippocampal epilepsy.

Animals↗
PubMed1999

Decreased calmodulin-NR1 co-assembly as a mechanism for focal epilepsy in cortical dysplasia.

The NMDA receptor is one of the ionotropic glutamate receptors essential for excitatory neurotransmission. The NMDAR1 subunit is inactivated by direct interaction with calmodulin. The protein levels of calmodulin, NMDAR1 and their complex were quantified in tissue resected from epileptogenic and non-epileptogenic cortical areas as determined by chronic subdural electrode recordings from three patients (aged 6, 14 and 18 years) with focal epilepsy associated with cortical dysplasia. In all patients, the co-assembly of calmodulin and NMDAR1 was decreased in epileptogenic dysplastic cortex compared with normal appearing non-epileptogenic cortex, while there was no significant difference in the total protein levels of calmodulin or NMDAR1 between the two EEG groups. These results suggest that decreased calmodulin-NMDAR1 co-assembly is a cellular mechanism that contributes to hyperexcitability in dysplastic cortical neurons and in focal seizure onsets.

Adolescent↗
PubMed1999

Time course of transient expression of GDNF protein in rat granule cells of the bilateral dentate gyri after unilateral intrahippocampal kainic acid injection.

We examined the time course of expression of glial cell line-derived neurotrophic factor (GDNF) protein in the granule cells of the dentate gyrus following unilateral intrahippocampal injection of kainic acid (KA). Recurrent behavioral seizures were observed approximately 1 h after KA injection, which lasted for 4-6 h. GDNF immunoreactivity began to increase bilaterally in the granule cells within 3 h after KA injection, continued to increase until post-injection day (PID) 4, and returned to the control level by PID 7. The results suggest that the increase of GDNF protein in the granule cells may be ascribable to seizures induced by the KA injection. The increase of GDNF protein might promote survival of the granule cells after the intrahippocampal KA injection.

Animals↗
PubMed1999

Selective coexpression of NMDAR2A/B and NMDAR1 subunit proteins in dysplastic neurons of human epileptic cortex.

NR1 and NR2 are the two gene families for the NMDA receptor. In vitro studies show that while NR2 alone is nonfunctional, NR1 alone produces weak currents to glutamate or NMDA. We previously showed by immunocytochemistry (ICC) that in normal appearing, nonepileptic human cortical neurons, only NR1 and not NR2 proteins were expressed, in contrast to the presence of both NR1 and NR2 in normal rat cortical neurons. We also showed, in dysplastic epileptic cortex, that both NR1 and NR2 were highly expressed using ICC on adjacent 30-microm sections. However, the relative coexpressions of NR1 and NR2 proteins in single neurons in single sections of human epileptic cortex were unknown. In this study, we used double-labeled immunofluorescence and confocal microscopy to examine the distribution and coexpression of subunit proteins for NR1 and NR2A/B in both nondysplastic (control comparison) and dysplastic regions of human brain resected for the treatment of intractable epilepsy (11 patients). In nondysplastic regions, cortical neurons did not have immunoreactivity (ir) for NR2A/B, whereas NR1-ir was abundant. By contrast, dysplastic neurons in the regions with epileptic cortical dysplasia showed intense NR2A/B-ir in the somata and their dendritic processes. These same NR2A/B-ir dysplastic neurons were colabeled by NR1. These results demonstrate directly that dysplastic neurons express both NR2A/B and NR1 proteins, whereas nondysplastic cortical neurons express only NR1 proteins. Selective coexpression of NR2A/B and NR1 in dysplastic neurons suggests that NR2A/B may form heteromeric NR1-NR2 coassemblies and hyperexcitability in dysplastic neurons that could contribute to focal seizure onset.

Animals↗
PubMed1999

Preoperative anal sphincter high pressure zone, maximum tolerable volume, and anal mucosal electrosensitivity predict early postoperative defecatory function after low anterior resection for rectal cancer.

PURPOSE: The aims of this study were to correlate postoperative defecatory function after low anterior resection with clinical factors and physiologic parameters and to explore the possibility of predicting early postoperative defecatory function after low anterior resection. METHODS: Thirty-two patients who underwent low anterior resection for rectal cancer were studied. Anorectal physiologic studies were performed preoperatively and six months postoperatively; maximum resting pressure, maximum squeeze pressure, length of the high pressure zone, neorectal sensory threshold, neorectal maximum tolerable volume, and anal mucosal electrosensitivity were recorded. Preoperative and postoperative defecatory function was scored between 0 (worst) and 6 (best) on the basis of bowel frequency, fecal incontinence, and urgency. RESULTS: In univariate regression analyses, a longer preoperative high pressure zone and a more sensitive anal mucosa were associated with better postoperative defecatory function. Using multiple regression analysis, in which age, gender, the level of anastomosis, and preoperative physiologic parameters were examined as independent variables, a longer preoperative high pressure zone, a larger preoperative maximum tolerable volume, and lower sensory threshold of the anal canal were associated with better postoperative defecatory function. Postoperative function score was found to be predictable using the following formula: 1.47 + 0.496 x high pressure zone (cm) + 0.007 x maximum tolerable volume (ml) - 0.247 x sensory threshold (mA) of the anal canal. CONCLUSION: Early postoperative defecatory function after low anterior resection is predictable from preoperative high pressure zone, maximum tolerable volume, and anal mucosal electrosensitivity.

Aged↗
PubMed1999

The role of the hippocampus in auditory processing studied by event-related electric potentials and magnetic fields in epilepsy patients before and after temporal lobectomy.

To clarify the relationship between the hippocampus and the event-related responses in auditory information processing, we recorded event-related potentials (ERPs) and event-related magnetic fields (ERFs) associated with the auditory oddball paradigm in 12 patients with temporal lobe epilepsy before and after surgical treatment, and in eight age-matched healthy volunteers. Lesions in the patients were hippocampal sclerosis (8), cyst (2), cavernoma (1) and calcified arteriovenous malformation (1), all in the unilateral temporal lobe. Standard temporal lobectomy (8), selective amygdalohippocampectomy (2), selective hippocampectomy (1) and inferior lateral temporal resection (1) were carried out. ERPs were recorded in nine patients before surgery, in all 12 patients after surgery, and in all normal subjects. P300 was maximal at Pz in the patients both before and after surgery, and in normal subjects. The peak latency and amplitude of P300 measured at Pz in the patients either before or after surgery did not differ significantly from those in normal subjects. After surgery, only the amplitude of P300 over the anterior and mid-temporal area on the resected side was attenuated, while it was symmetric before surgery regardless of the side of epileptogenic focus. ERFs were recorded in three patients before surgery and in six normal subjects by using a whole-head neuromagnetometer. ERFs in response to the target stimuli at a latency of approximately 400 ms were recognized at the anterior, middle and posterior lateral channels on each hemisphere (M400). The latency and dipole moments for M400 did not differ significantly between the patients before surgery and the normal subjects. As a result of analysis using the time-varying multidipole model, three dipoles for M400 were estimated in two patients in whom ERFs were available before surgery for the analysis, and in normal subjects: mesial temporal area, superior temporal area and inferior parietal area on each hemisphere. After surgery, in four out of six patients in whom ERFs were recordable, M400 at the anterior temporal channels on the resected side disappeared, and the activity in the affected mesial temporal area was lost. In one patient who underwent inferior lateral temporal resection, M400 waveforms and its sources were preserved in all regions. There were no significant differences in the latency and dipole moments of the unaffected source of M400 before versus after surgery. These results suggest that the hippocampus contributes to the scalp-recorded P300 only at the corresponding anterior temporal region, and does not influence its general waveform and predominant distribution over the scalp.

Adult↗
PubMed1999

Focal ictal direct current shifts in human epilepsy as studied by subdural and scalp recording.

In order to clarify further the characteristics of ictal direct current (DC) shifts in human epilepsy, we investigated them by subdural and scalp recording in six and three patients, respectively, both having mainly neocortical lobe epilepsy (five with frontal lobe epilepsy, two with parietal lobe epilepsy and two with temporal lobe epilepsy). By using subdural electrodes made of platinum, ictal DC shifts were observed in 85% of all the recorded seizures (89 seizures) among the six patients, and they were localized to just one or two electrodes at which the conventional initial ictal EEG change was also observed. They were closely accompanied by the electrodecremental pattern in all patients except for one in whom 1 Hz rhythmic activity was superimposed on clear negative slow shifts. Seizure control after resection of the cortex, including the area showing DC shifts, was favourable irrespective of histological diagnosis. Scalp-recorded ictal slow shifts were observed in 23% of all the recorded seizures (60 seizures) among the three patients. They were, like the subdurally recorded ones, mainly surface-negative in polarity, closely related to the electrodecremental pattern and consistent in their location. It seems that scalp-recorded DC shifts were detected particularly when seizures were clinically intense, while no slow shifts were observed in small seizures. It is concluded that at least subdurally recorded ictal slow shifts are clinically useful before epilepsy surgery to delineate more specifically an epileptogenic area as well as to further confirm the conventional initial ictal EEG change, and that scalp-recorded ictal slow shifts also have high specificity although their low sensitivity is to be taken into account.

Adolescent↗
PubMed1999

Cognitive motor control in human pre-supplementary motor area studied by subdural recording of discrimination/selection-related potentials.

To clarify the functional role of human pre-supplementary motor area (pre-SMA) in 'cognitive' motor control as compared with other non-primary motor cortices (SMA-proper and lateral premotor areas) and prefrontal area, we recorded epicortical field potentials by using subdural electrodes in five epileptic patients during presurgical evaluation, whose pre-SMA, SMA-proper, prefrontal and lateral premotor areas were defined by electric cortical stimulation and recent anatomical orientations according to the bicommissural plane and callosal grid system. An S1-Go/NoGo choice and delayed reaction task (S1-choice paradigm) and a warned choice Go/NoGo reaction task (S2-choice paradigm) with inter-stimulus intervals of 2 s were employed. The results showed (i) transient potentials with onset and peak latencies of about 200 and 600 ms, respectively, after S1 in the S1-choice paradigm mainly at pre-SMA and to a lesser degree at the prefrontal and lateral premotor areas, but not in the S2-choice paradigm. At SMA-proper, a similar but much smaller potential was seen after S1 in both S1- and S2-choice paradigms and (ii) slow sustained potentials between S1 and S2 in both S1- and S2-choice paradigms in all of the non-primary motor areas investigated (pre-SMA, SMA-proper and lateral premotor areas) and prefrontal area. It is concluded that pre-SMA plays a more important role in cognitive motor control which involves sensory discrimination and decision making or motor selection for the action after stimuli, whereas SMA-proper is one of the main generators of Bereitschaftspotential preceding self-paced, voluntary movements. In the more general anticipation of and attention to the forthcoming stimuli, non-primary motor cortices including pre-SMA, SMA-proper and lateral premotor area, and the prefrontal area are commonly involved.

Adult↗
PubMed1999

NMDA-receptors 1 and 2A/B coassembly increased in human epileptic focal cortical dysplasia.

PURPOSE: This study was designed to quantify the relation between expressions of NMDA receptor (NMDAR) subunits (1 and 2A/B) and the epileptogenicity in human focal cortical dysplasia. METHODS: Immunoblotting and immunoprecipitation were used to quantify these receptor subunits in tissue resected from EEG-verified epileptic and distal nonepileptic frontal cortical areas in each of three patients as determined by chronic subdural electrode recordings. In each patient, adjacent sections were immunostained to verify that the numbers of dysplastic neurons were greater in epileptic than in nonepileptic cortex. RESULTS: In all patients, NMDAR2A/B expressions and their coassemblies with NMDAR1 were increased in epileptic dysplastic cortex compared with the relatively normal appearing nonepileptic cortex. For all three patients, there were no significant differences in NMDAR1 protein expressions between the two EEG groups. CONCLUSIONS: These results suggest that increased NMDAR1-NMDAR2A/B coassembly contributes to hyperexcitability in dysplastic cortical neurons and focal seizure onsets.

Adolescent↗
PubMed1998

Postnatal expressions of non-phosphorylated and phosphorylated neurofilament proteins in the rat hippocampus and the Timm-stained mossy fiber pathway.

Neurofilament proteins (NFPs), the cytoskeletal proteins that are essential for axogenesis and maintenance of neuron shape in the nervous system, were studied for their spatial distributions at nine postnatal days (PN 3, 5, 7, 10, 14, 17, 21, 28, and 120). Simultaneously non-phosphorylated (SMI-32; 150/200 kDa; Sternberger) and phosphorylated (SMI-31; 200 kDa) NFP immunoreactivity in the entire developing rat hippocampus was studied, quantified, and compared to that of mossy fiber (MF) axons and terminals using Neo-Timm's histochemistry, the most selective, sensitive, and reproducible technique. Differential developmental expressions were observed between the two NFP states. SMI-32 was initially expressed on PN 3 only in the perikarya of pyramidal neurons in CA3. As early as PN 5, SMI-31 appeared in the MF pathway, in parallel to the growth of MF axons. By contrast, SMI-32 did not appear at any age in the MF pathway, including the MF terminal zone of stratum lucidum. At PN 14, the distribution of both NFPs in the MF system (MFs and their target neurons, i.e., CA3/CA4 pyramidal neurons and hilar neurons) was nearly complete; however, the peak densities of SMI-32 and SMI-31 were later at PN 21 and statistically equal to the most adult level (PN 120). The temporal regulation and maximal levels of SMI-32 and SMI-31 expressions on MF target neurons (CA3: SMI-32) and in the MF terminal zone (stratum lucidum: SMI-31) were nearly parallel to the progressive and rapid PN growth of the MF axons and terminals occurring between PN 14 and PN 17, suggesting that the mechanisms for maturation of MF synaptogenesis occur after PN 17.

Animals↗
PubMed1998

A short episode of seizure activity protects from status epilepticus-induced neuronal damage in rat brain.

Kainic acid (KA)-induced status epilepticus (SE) in adult rats results in extensive neuronal damage throughout the limbic system and the loss of selectively vulnerable neuronal populations, particularly CA3 neurons. We investigated the effects of a short episode of seizure activity on neuronal death elicited by a subsequent prolonged SE episode. A short episode of seizure activity was produced by sub-cutaneous (s.c.) injection of KA followed after 1 h by pentobarbital administration. Twenty-four hours later, KA was administered again, and animals were sacrificed 3 days later. Neuronal damage was estimated by visual analysis of neuronal density. Our results show that a short episode of seizure activity did not produce neuronal damage but almost completely protected vulnerable neurons from KA-induced neuronal damage. These results extend to epileptic tolerance the notion of tolerance previously described in the case of ischemia.

Animals↗