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The present study characterized quantitatively sexual dimorphic development of gyrification by MRI-based morphometry. High spatial-resolution 3D MR images (using RARE sequence with short TR and minimum TE setting) were acquired from fixed brain of male and female ferrets at postnatal days (PDs) 4-90 using 7-tesla preclinical MRI system. The gyrification index was evaluated either throughout the cerebral cortex (global GI) or in representative primary sulci (sulcal GI). The global GI increased linearly from PD 4, and reached a peak at PD 42, marking 1.486±0.018 in males and 1.460±0.010 in females, respectively. Sexual difference was obtained by greater global GI in males than in females on PD 21 and thereafter. Rostrocaudal GI distribution revealed an overall male-over-female sulcal infolding throughout the cortex on PD 21. Then, an adult pattern of sexually dimorphic cortical convolution was achieved so that gyrification in the temporo-parieto-occipital region was more progressive in males than in females on PD 42, and slightly extended posteriorly in males until PD 90. In the sulcal GI, sulcus-specific male-over-female GI was revealed in the rhinal fissure, and presylvian sulcus on PD 42, and additionally in the coronal, splenial, lateral, and caudal suprasylvian sulci on PD 90. The current results suggest that age-related sexual dimorphism of the gyrification was biphasic in the ferret cortex. A male-over-female gyrification was allometric by PD 21, and was thereafter specific to primary sulci located on phylogenetically newer multimodal cortical regions., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to quantitatively clarify differences in laminar structure and myeloarchitecture of sulcal and gyral regions of the cerebral cortex of ferrets. Histological sections of cerebrum from male and female ferrets at postnatal day 90 were made at the coronal plane, and were immunostained with anti-NeuN or anti-myelin basic protein (MBP). Thickness was estimated in the entire depth or three strata, that is, layer I, outer (layers II-III) and inner (layers IV-VI) strata of the neocortex in representative five sulcal and seven gyral regions. As with the entire cortical depth, outer and inner strata were significantly thinner in the sulcal bottoms than in the gyral crowns, whereas layer I had about twofold greater thickness in the sulcal bottoms. However, thicknesses of the entire cortical depth and each cortical stratum were not statistically different among five sulcal regions or seven gyral regions examined. By MBP immunostaining, myelin fibers ran tangentially through the superficial regions of layer I in gyral crowns. Those fibers were relatively denser in gyri of frontal and temporal regions, and relatively sparse in gyri of parietal and occipital regions, although their density in any gyri was not different between sexes. These results show a differential laminar structure and myeloarchitecture between the sulcal and gyral regions of the ferret cerebral cortex present in both sexes. Myelination of layer I tangential fibers varied among primary gyri and was weaker in phylogenetically higher-order cortical gyri. Anat Rec, 299:1003-1011, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The present study characterized fetal sulcation patterns and gyrification in the cerebrum of the New World monkey group, common marmosets, using a 3D T2-weighted high-resolution anatomical magnetic resonance imaging (MRI) sequence from the fixed brain at 7-tesla ex vivo. Fetal sulcation in the marmoset cerebrum began to indent the lateral fissure and hippocampal sulcus in gestational week (GW) 12, and then the following sulci emerged: the callosal and calcarine sulci on GW 15; the superior temporal sulcus on GW 17; and the circular and occipitotemporal sulci on GW 18. The degree of cortical convolution was evaluated quantitatively based on 2D MRI slices by the gyrification index (GI) and based on 3D MRI data by sulcation index (SI). Both the mean GI and SI increased from GW 16, and were closely correlated with the cortical volume and the cortical surface area during fetal periods (their correlation coefficients marked more than 0.95). After birth, both the mean GI and SI decreased slightly by 2years of age, whereas the cortical volume and surface area continuously increased. Notably, histological analysis showed that the outer subventricular zone (oSVZ) in non-sulcal regions was thicker than that in the presumptive calcarine sulcal region on GW 13, preceding the infolding of the calcarine sulcus. The present results showed definite sulcal infolding on the cerebral cortical surface of the marmosets, with similar pattern and sequence of their emergences to other higher-order primates such as macaques and humans. Differential expansion of the oSVZ may be involved in gyral convolution and sulcal infolding in the developing cerebrum., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to quantitatively characterize structural abnormalities of the cerebrum in a growth-retarded mouse (grt/grt) with a tyrosylprotein sulfotransferase 2 gene defect. Three-dimensional computed tomography (CT) images were obtained from fixed brains of male homogenous grt/grt (n=5) and heterozygous grt/+ (n=5) mice at 15 weeks of age, and volumes of representative cerebral regions were calculated on the basis of those images. Following CT measurements, cryosections of the brain were made, and immunohistochemistry for NeuN and SMI-32 was carried out. By CT-based volumetry, region-specific reductions in volumes were marked in the cerebral cortex and white matter, but not in other cerebral regions of grt/grt. When quantitatively evaluating the shape of the cerebral cortex, the frontooccipital length of the cortex was significantly smaller in grt/grt than in grt/+, whereas the cortical width was not altered in grt/grt. On the other hand, both cortical thickness and density of NeuN-immunopositive neurons in three distinctive cortical regions, i.e., the primary motor cortex, barrel field of primary somatosensory cortex and primary visual cortex, were not different between grt/grt and grt/+. By semi-quantitative immunohistochemical analysis, the intensity of SMI-32 immunostaining was significantly weaker in grt/grt than in grt/+ in the three cortical areas examined. SMI-32 staining was reduced, particularly in layer III pyramidal neurons in grt/grt, while it was sustained in multipolar neurons. The present results suggest that cerebral abnormalities in grt/grt mice are characterized by cortical hypoplasia at the frontooccipital axis with immature pyramidal neurons and insufficient development of callosal fibers.

The present study aimed to characterize cerebral morphology in young adult ferrets and its sexual dimorphism using high-field MRI and MRI-based morphometry. Ex vivo short TR/TE (typical T1-weighted parameter setting for conventional MRI) and T2W (long TR/TE) MRI with high spatial resolution at 7-tesla could visualize major subcortical and archicortical structures, i.e., the caudate nucleus, lentiform nucleus, amygdala and hippocampus. In particular, laminar organization of the olfactory bulb was identifiable by short TR/TE-MRI. The primary and secondary sulci observable in the adult ferret were distinguishable on either short TR/TE- or T2W-MRI, and the cortical surface morphology was reproduced well by 3D-rendered images obtained by short TR/TE-MRI. The cerebrum had a significantly lower volume in females than in males, which was attributed to region-specific volume reduction in the cerebral cortex and subcortical white matter in females. A sexual difference was also detected, manifested by an overall reduction in normalized signal ratios of short TR/TE-MRI in all cerebral structures examined in females than in males. On the other hand, an alternating array of higher and lower short TR/TE-MRI intensity transverse zones throughout the cortex, which was reminiscent of the functional cortical areas, was revealed by maximum intensity projection (MIP) in 3D. The normalized signal ratio of short TR/TE-MRI, but not T2W-MRI in the cortex, was negatively correlated with the density of myelin-basic protein immunoreactive fibers (males, r=-0.440; females, r=-0.481). The present results suggest that sexual differences in the adult ferret cerebrum are characterized by reduced volumes of the cerebral cortex and subcortical white matter in females, and by overall reductions in physiochemical characteristics, as obtained by short TR/TE-MRI, in females. It should be noted that short TR/TE-MRI-based MIP delineated functional cortical areas related to myeloarchitecture in 3D. Such an approach makes possible conventional investigation of the functional organization of the cerebral cortex and its abnormalities using high-field MRI., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The present study aimed to clarify sulcation and gyration patterns in the developing cerebrum of ferrets. While the brain weight and fronto-occipital length of the cerebral hemisphere reached a plateau by postnatal day (PD) 42, the cerebral width reached a plateau at the rostral region by PD 21, and subsequently at the caudal region by PD 42. The ferret cerebrum already showed a convoluted surface with indentations of coronal and rostral suprasylvian sulci on PD 4. The presylvian and cruciate sulci emerged by PD 10, resulting in convolutions of gyri in the rostral half of the cerebrum. The caudal half of the cerebrum was infolded by the emergence of the pseudosylvian sulcus and the rhinal fissure by PD 10, and the caudal suprasylvian and lateral sulci by PD 21. The emergence of those sulci allowed a gyration in the caudal half of the cerebrum. Sexual differences in sulcation were detected by a more distinct convolution of the visual cortex in males than in females on PD 90. Those results, therefore, suggest that the ferret cerebrum experiences cortical maturation with sulcation and gyration in a rostrocaudal gradient manner. The present paper provides neuroanatomic references for normal development of cerebral sulci and gyri in both sexes of ferrets., (© 2012 The Authors. Congenital Anomalies © 2012 Japanese Teratology Society.)

Our article summarizes a series of studies about fetal gyrification and its relation to cerebral growth in cynomolgus monkeys. Based on the cerebral growth (i.e., brain weight, cerebral volume, and frontooccipital length of the cerebral hemisphere) and the developmental pattern of gyrification in each sulcus of cynomolgus monkeys, we divided the gyrification process into four stages: Stage 1. Demarcation of cerebral lobes and limbic gyri; Stage 2. Demarcation of neocortical gyri; Stage 3. Emergence of secondary and tertiary sulci; and Stage 4. Growth of sulcal length and depth. Each stage of those gyrification processes was influenced by different developmental events, such as the emergence of corticocortical long-associative fiber tracts, cortical maturations, and subcortical white-matter development. This is the first report to systematically propose gyrification processes closely related to the order of phyologenetical development of the cerebral cortex in primates., (Copyright © 2012 Wiley Periodicals, Inc.)

In the present study developmental changes in the cerebral sulci and volumes of subcortical and archicortical structures of the cerebrum in cynomolgus monkey fetuses were examined with T(1)-weighted magnetic resonance (MR) images in 3D. On the embryonic day (ED) 90, the lateral ventricle had still an immature vesicular shape in the occipital region of the cerebrum, and it dramatically closed its lumen by ED 100. In that period the calcarine sulcus progressively infolded from the medial surface of the cerebral hemisphere narrowing the lumen of the lateral ventricle in the occipital region. Volume of the lateral ventricle decreased in the period ED 90-100, increasing afterwards in spite of increasing volumes of subcortical and archicortical structures such as the caudate nucleus, putamen, globus pallidus, amygdala and hippocampal formation. During the same time, the volume of the germinal matrix around lateral ventricles decreased to disappear completely by ED 120. These results suggest that the morphological maturation of lateral ventricle is linked to the development of calcarine sulcus in cynomolgus monkey fetuses. The degree of infolding of calcarine sulcus on ED 100 would be useful as a gross anatomical landmark for evaluating the cerebral maturation in cynomolgus monkey fetuses.

The ontogenetic pattern of gyrification and its relationship with cerebral cortical volume were examined in cynomolgus monkey fetuses. T(1)-weighted coronal magnetic resonance (MR) images at 7 T were acquired from the fixed cerebra of three male fetuses, each at embryonic days (EDs) 70 to 150, and the gyrification index (GI) of each slice was estimated. The mean GI was low (1.1-1.2) during EDs 70 to 90, and then increased dramatically on ED 100. The developmental profiles of the rostrocaudal GI distribution revealed that cortical convolution was more frequent in the parietooccipital region than in other regions during EDs 100 to 150, forming an adult-like pattern by ED 150. The mean GI was closely correlated with the volume of cortical gray matter (r=0.9877), and also with the volume of white matter/intermediate zone (r=0.8961). These findings suggest that cortical convolution is correlated with either the maturation of cortical gray matter or the development of white matter bundles. The characteristic GI distribution pattern of catarrhines was formed by ED 150 in correlation with the progressive sulcal infolding in the parietooccipital region of the cerebrum., (Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)

This study aimed to clarify chronological sequences of the appearances of sulci and gyri on the medial cerebral surface and its relation to the regional development of the cerebrum in cynomolgus monkeys. The lengths of cingulate and calcarine sulci were measured, and the ratios of these lengths to fronto-occipital length were estimated as indices of the size of the "frontoparietal" and "occipital" regions, respectively. The relative length of cingulate sulcus showed a biphasic increase: a slow phase from EDs 100 to 110, and a rapid phase from EDs 110 to 130. The gyri in the "frontoparietal region" were convoluted in the limbic cortex during the initial slow phase and in the neocortical region during the rapid phase. The relative length of calcarine sulcus lineally increased between EDs 90 and 130, and the gyri in the "occipital region" generated in a dorso-ventral manner: the gyrus convolutions occurred first in the "phylogenetically older" striate and dorsal extrastriate cortices, and then in the "phylogenetically newer" ventral extrastriate cortex. The results suggest that the chronological order of appearance of sulci and gyri is closely associated with the order of phylogenetical development of the cerebral cortex. The present study provides a standard reference for the development of cerebral sulci and gyri of cynomolgus monkeys together with our previous study (Fukunishi et al. Anat Embryol 211:757-764, 2006).

Long-lasting membrane depolarization in cerebral ischemia causes neurotoxicity via increases of intracellular sodium concentration ([Na+]i) and calcium concentration ([Ca2+]i). Donepezil has been shown to exert neuroprotective effects in an oxygen-glucose deprivation model. In the present study, we examined the effect of donepezil on depolarization-induced neuronal cell injury resulting from prolonged opening of Na+ channels with veratridine in rat primary-cultured cortical neurons. Veratridine (10 microM)-induced neuronal cell damage was completely prevented by 0.1 microM tetrodotoxin. Pretreatment with donepezil (0.1-10 microM) for 1 day significantly decreased cell death in a concentration-dependent manner, and a potent NMDA receptor antagonist, dizocilpine (MK801), showed a neuroprotective effect at the concentration of 10 microM. The neuroprotective effect of donepezil was not affected by nicotinic or muscarinic acetylcholine receptor antagonists. We further characterized the neuroprotective properties of donepezil by measuring the effect on [Na+]i and [Ca2+]i in cells stimulated with veratridine. At 0.1-10 microM, donepezil significantly and concentration-dependently reduced the veratridine-induced increase of [Ca2+]i, whereas MK801 had no effect. At 10 microM, donepezil significantly decreased the veratridine-induced increase of [Na+]i. We also measured the effect on veratridine-induced release of the excitatory amino acids, glutamate and glycine. While donepezil decreased the release of glutamate and glycine, MK801 did not. In conclusion, our results indicate that donepezil has neuroprotective activity against depolarization-induced toxicity in rat cortical neurons via inhibition of the rapid influx of sodium and calcium ions, and via decrease of glutamate and glycine release, and also that this depolarization-induced toxicity is mediated by glutamate receptor activation.

The present study examined the effect of electro-acupuncture stimulation of PC5 and PC6, acupuncture points located on the pericardium meridian, on electroencephalogram (EEG) changes, bioimpedance value, and electrocardiogram (ECG) heart rate. The EEGs of the frontal, central, temporal, parietal, and occipital lobes were measured. Generally, the EEGs increased at large amplitude in the all lobe during electro-acupuncture (EA) stimulation of PC5 and PC6. According to the present experiments, after the EA stimulation of PC5, EEG was verified to change at an extremely large amplitude in the temporal lobe. A comparison of biological active points (BAPs) and non-BAPs in bioimpedance measurement experiments revealed that reactance resistance had low-resistance characteristics and characteristics frequency had frequency characteristics. The ECG heart rate decreased at PC6 and increased at PC5. PC6 therefore may have a certain effect on sedation of the human nervous system. We applied CWT to detect short-time event and the result image representation of the signal has showed us that one can easily find the discontinuity at the time scale representation. The results of the present study verified that the EA stimulation of BAPs (PC5, PC6) affects EEG, human bioimpedance, and ECG heart rate, and such stimulation may be capable of affecting the nervous system.

Poor detection of muscle motor evoked potential (m-MEP) by electrical cortical stimulation has often been encountered during neurosurgical operations, although widely known optimal factors for reliable detection have been put into practice. We hypothesized that the depth of anesthesia influenced the detection of m-MEP. Bispectral Index (BIS) monitoring was used to assess the depth of anesthesia for 16 patients during brain tumor operations. The doses of intravenous anesthetics, propofol, were titrated according to BIS indices during operations. When BIS indices were 40 or below, detection was difficult and higher intensities of electrical stimulation were necessary to evoke m-MEPs. Furthermore, risk of seizure was relatively high due to stronger electrical stimulation. Our results suggested that a BIS index above 50 and below 70 was optimal range. BIS monitoring is a useful method for setting the optimal dose of anesthetics for reliable intraoperative cortical mapping.

In the present study, we administered liquid diets containing ethanol to pregnant rats on different schedules, and examined the cerebral cortex of their pups on gestational day (GD) 21 by immunohistochemistry. The first group of pregnant rats was fed a liquid diet containing 5% (w/v) ethanol during GDs 10-21(5% Et). The second group was fed a liquid diet containing 2.5% (w/v) ethanol on GDs 10-12, a diet containing 4% (w/v) ethanol on GDs 13-15, and a diet containing 5% (w/v) ethanol on GDs 16-21 (2.5-5% Et). Pups of 5% Et dams had leptomeningeal heterotopias mainly in the parietal cortex. In 2.5-5% Et pups, other types of malformations such as grooves, microgyri, stacked-up cortices, and defects of layer I were found. The diet intake and body weight gain of 2.5-5% Et dams were significantly higher than those of 5% Et dams during GDs 11-16. There was no difference in total ethanol consumption during GDs 10-21 between the two groups. However, ethanol consumption on GD 15 in 2.5% Et was higher than in 5% Et. A different schedule for administration of an ethanol-containing diet in pregnancy might induce different types of cerebral malformations in rat fetuses.

Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. This process is guided by radial glial fibers, requires proper receptors, ligands, other unknown extracellular factors, and local signaling to stop neuronal migration. This process is also highly sensitive to various physical, chemical and biological agents as well as to genetic mutations. Any disturbance of the normal process may result in neuronal migration disorder. Such neuronal migration disorder is believed as major cause of both gross brain malformation and more special cerebral structural and functional abnormalities in experimental animals and in humans. An increasing number of instructive studies on experimental models and several genetic model systems of neuronal migration disorder have established the foundation of cortex formation and provided deeper insights into the genetic and molecular mechanisms underlying normal and abnormal neuronal migration.

Pregnant rats were fed an ethanol-containing liquid diet between gestational day (GD) 10 and GD 21. Leptomeningeal heterotopias were observed in the cerebral cortex of ethanol-exposed fetuses. They appeared on the brain surface of the lateral cortical region near the rhinal fissure, and were found more numerously in the rostral than the caudal region. These abnormalities contained certain neuronal perikarya, microtubule-associated protein (MAP) 1b-positive neuronal processes, and Rat-401-positive radial glial fibers. Immunostaining for Rat-401 revealed that the heterotopias protruded through breaches in the glia limitans. In adult rats exposed to ethanol prenatally, the heterotopias persisted in the lateral cortical region. We conclude that prenatal exposure to ethanol might induce defects in the glia limitans, resulting in the genesis of leptomeningeal heterotopias. These abnormalities may be related to mental retardation or the cognitive deficits associated with human fetal alcohol syndrome (FAS).

We characterized the electrophysiological properties of calcium channels in cultured rat cerebral cortical neurons using omega-agatoxin-TK (omega-Aga-TK) by a patch-clamp technique. Two types of slowly inactivating calcium channels sensitive to omega-Aga-TK were detected. The first type showed high sensitivity to omega-Aga-TK and low recovery from the omega-Aga-TK-induced blockade during washout, corresponding to the P-type channel. The second type showed low sensitivity to omega-Aga-TK and high recovery, resembling the Q-type channel, although it was distinct from the Q-type in terms of slower inactivation kinetics. We designate this channel as Q(L)-type (long-lasting Q channel). The omega-Aga-TK-sensitive calcium channels involved in the glutamatergic synaptic transmission were also divided into two types based on the sensitivity to omega-Aga-TK and reversibility of omega-Aga-TK-induced blockade. We conclude that the Q(L)-type is a novel type of channel, and that both P-type and Q(L)-type channels play a significant role in the cerebral cortical synaptic transmission.

When low frequency electrical stimulations were repeatedly applied to the rat midbrain reticular formation, the EEG spectral power recorded at the cortex and thalamus increased markedly, especially in the low frequency bands (0-6 Hz). The intraventricular administration of histamine (Hi) inhibited this increase. Hi-induced inhibition was antagonized by simultaneous injection of an equimolar dose of either pyrilamine or diphenhydramine, but not by that of cimetidine. In accordance with this, 2-methylHi decreased the power in the slow wave region, while 4-methylHi was not effective. It was assumed that the EEG arousal effect of Hi is exerted via H1 receptors but not related to H2 receptors. Adverse effects of H1 blockers on the brain, such as drowsiness, may be produced as a consequence of this inhibitory action.

To clarify whether the sedative effect of H1 blockers is exerted in relation to H1 receptors in the brain, EEG activity recorded from the cortex and thalamus of rats was studied by power spectral analysis. EEG processing was performed by the FFT method and displayed as compressed spectral arrays. When a train of low frequency electrical stimulation was applied to the midbrain reticular formation of conscious rats, there was an increase in spectral power recorded at the cortex and thalamus, especially in the low frequency bands (0-6 Hz). The intraventricular administration of histamine suppressed the increase in power; this inhibition was antagonized by simultaneous administration of pyrilamine or diphenhydramine, though not in in combination with cimetidine or ranitidine. As in the case of histamine, the administration of 2-methylhistamine decreased power in the slow wave region, while administration of 4-methylhistamine did not. It was assumed that the arousal effect of histamine is exerted via H1 and not related to H2 receptors. Adverse effects of H1 blockers, such as drowsiness, may be caused by their inhibition of histamine's arousal effect.