Abstract: Summary Purpose: To analyze cellular mechanisms of limbic-seizure suppression, the response to pilocarpine-induced seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods: Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of seizures lasting 3 h. Subpopulations of gamma-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results: In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10-20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when <30% of reticular nucleus cells were Fos-positive, and then decreased, with no relationship with cell loss, evaluated in Nissl-stained sections. In Proechimys, almost all reticular nucleus neurons were Fos-positive at 24 h. Discussion: At variance with laboratory rats, pilocarpine-induced protracted seizures elicit in Proechimys limited neuronal death, and marked and long-lasting Fos induction in excitatory and inhibitory cortical and thalamic cell subsets. The findings implicate intrathalamic and intracortical regulation, and circuits linking thalamus and cortex in limbic seizure suppression leading to epilepsy resistance.

Abstract: OBJECTIVES: To assess the effect of mild forced physical training on cognitive and locomotory behavior in old (26 mo.) mice. DESIGN: Randomized, controlled study. SETTING: Open-field in the behavioral laboratory. PARTICIPANTS: Sixteen old sedentary male mice randomly assigned to one of two groups, exercise (E) or rest (R). INTERVENTION: group E underwent treadmill running for one month at moderate intensity (belt speed=8 m/min, 45 min, five days a week), group R was only allowed spontaneous locomotor activity. MEASUREMENTS: exploratory and locomotor behavior were evaluated in an enriched environment (Ethovision recording). RESULTS: motor patterns were significantly reduced (chi2 test, p<0.05) in the E vs R group after one month of training; exploratory patterns were not different, both groups showing modest exploratory activity. CONCLUSIONS: mild forced physical training initiated at old age may have detrimental effect on motor behavior in male mice without improving cognitive parameters.

Abstract: A 41-year-old woman with focal epilepsy was analyzed immediately and 1 week post-ictally using pulsed-arterial-spin-labeling perfusion 3T MRI, a non-invasive method. Seizure-associated blood flow alterations were characterized by increased ictal perfusion in the occipito-parietal right cortex, and hypoperfusion in the same location 1 week later. These results indicate that non-invasive perfusion MRI can be used routinely to detect vascular alterations in epilepsy, and possibly to identify the location of the seizure focus.

Abstract: The mechanisms involved in the pathogenesis of epilepsy, a chronic neurological disorder that affects approximately one percent of the world population, are not well understood. Using a mouse model of epilepsy, we show that seizures induce elevated expression of vascular cell adhesion molecules and enhanced leukocyte rolling and arrest in brain vessels mediated by the leukocyte mucin P-selectin glycoprotein ligand-1 (PSGL-1, encoded by Selplg) and leukocyte integrins alpha(4)beta(1) and alpha(L)beta(2). Inhibition of leukocyte-vascular interactions, either with blocking antibodies or by genetically interfering with PSGL-1 function in mice, markedly reduced seizures. Treatment with blocking antibodies after acute seizures prevented the development of epilepsy. Neutrophil depletion also inhibited acute seizure induction and chronic spontaneous recurrent seizures. Blood-brain barrier (BBB) leakage, which is known to enhance neuronal excitability, was induced by acute seizure activity but was prevented by blockade of leukocyte-vascular adhesion, suggesting a pathogenetic link between leukocyte-vascular interactions, BBB damage and seizure generation. Consistent with the potential leukocyte involvement in epilepsy in humans, leukocytes were more abundant in brains of individuals with epilepsy than in controls. Our results suggest leukocyte-endothelial interaction as a potential target for the prevention and treatment of epilepsy.

Abstract: Brain atrophy has consistently been observed in schizophrenia, representing a 'gross' evidence of anatomical abnormalities. Reduced cerebral blood volume (CBV) may accompany brain size decrement in schizophrenia, as suggested by prior small SPECT studies. In this study, we non-invasively investigated the hemisphere CBV in a large sample of patients suffering from schizophrenia with perfusion-weighted imaging (PWI). PWI images were obtained, following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), for 54 DSM-IV patients with schizophrenia (mean age+/-SD=39.19+/-12.20 years; 34 males, 20 females) and 24 normal controls (mean age+/-SD=44.63+/-10.43 years; 9 males, 15 females) with a 1.5T Siemens magnet using an echo-planar sequence (TR=2160 ms, TE=47 ms, slice thickness=5mm). The contrast of enhancement (CE), a semi-quantitative parameter inversely estimating the CBV, were calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/Sox100) for right and left hemisphere on two axial images. Specifically, higher CE values correspond to lower CBV and viceversa Compared to normal controls, patients with schizophrenia had significantly higher bilateral hemisphere CE values (p=0.02) and inverse CE laterality index (p=0.02). This study showed abnormally reduced and inverse hemisphere CBV in a large population of patients with schizophrenia. Hypothetically, chronic low CBV may sustain neural hypoactivation and concomitant increase of free radicals, ultimately resulting in neuronal loss and cognitive impairments. Thus, altered intracranial hemodynamics may accompany brain atrophy and cognitive deficits, being a crucial factor in the pathophysiology of schizophrenia.

Abstract: The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE). Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE) degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology.

Abstract: A new type of magnetic resonance imaging analysis, based on fusion of three-dimensional reconstructions of time-to-peak parametric maps and high-resolution T1-weighted images, is proposed in order to evaluate the perfusion of selected volumes of interest. Because in recent years a wealth of data have suggested the crucial involvement of vascular alterations in mental diseases, we tested our new method on a restricted sample of schizophrenic patients and matched healthy controls. The perfusion of the whole brain was compared with that of the caudate nucleus by means of intrasubject analysis. As expected, owing to the encephalic vascular pattern, a significantly lower time-to-peak was observed in the caudate nucleus than in the whole brain in all healthy controls, indicating that the suggested method has enough sensitivity to detect subtle perfusion changes even in small volumes of interest. Interestingly, a less uniform pattern was observed in the schizophrenic patients. The latter finding needs to be replicated in an adequate number of subjects. In summary, the three-dimensional analysis method we propose has been shown to be a feasible tool for revealing subtle vascular changes both in normal subjects and in pathological conditions.

Abstract: Type III cells of the taste organs are widely considered to be chemoreceptors. The present study was performed on the frog taste disk and describes an axon-like process in type III cells, which often contains a bundle of densely-packed parallel microfilaments. These processes pass through the basal membrane of the gustatory epithelium, running into the lamina propria (transbasal membrane processes, tBMPs). In their intraepithelial tract, tBMPs contain dense-cored vesicles revealing their origin from type III cells. Type III cells showing both classic nonrigid processes (with vesicles and nerve contacts) and tBMPs are present. The connective tract of a tBMP usually contains dense-cored vesicles only in its proximal portion. In some cases, the connective tract of tBMPs is almost perpendicular to the basal lamina. In other cases, it runs parallel to and below the basal lamina. Some tBMPs contact nerve fibers running in the subepithelial connective tissue; the contact area is rather wide but evident synapse-like junctions were never detected. Contacts between tBMPs and nerve fibers innervating basal cells are also found. In conclusion, the data demonstrate the existence of epithelial cells resembling primitive neurons that display an apical dendrite and axon-like basal processes. Until now, it was not considered possible that epithelial receptor cells extend processes out of the epithelium.

Abstract: The hydrolipidic ratio (HLR) expresses the amount of water and fat in a tissue. HLR can be studied non-invasively in the living organism and can be mapped in different areas of the body with high spatial and temporal resolution. In the present work we have evaluated the HLR in different adipose tissue depots in young or adult rats using tissue arrays of fat fragments by 1H-spectroscopy. In young animals, the highest percentage of water (33%) was found in the interscapular brown adipose tissue (iBAT). Mesenteric fat (mWAT) also appeared highly hydrated (24%). The deposits composed of epididymal, retroperitoneal and pelvic white adipose tissue (eWAT, rWAT and pWAT, respectively) contained an amount of water ranging from 14% to 17%. In adult animals, a reduction of the water content was found in all the depots. In e/r/pWAT, the age-related maturation was characterized by large changes in adipocyte diameter accompanied by a small change in HLR. In the iBAT, the maturation was accompanied by small change in adipocyte diameter and a greater diminution of HLR. mWAT showed an intermediate pattern between e/r/pWAT and iBAT. In all the studied depots, an age-related increase in leptin expression was found. This increase was relatively low in iBAT (40%) and high in the e/r/pWAT (204-273%). The work expand the knowledge about the physiological significance of the HLR by 1H-spectroscopy.

Abstract: Structural and functional MRI was used in conjunction with computerized electron microscopy morphometry to study changes 2 h, 24 h and 3 days after 4-aminopyridine-induced seizures lasting 2 h in rats. T2 (relaxation time) values showed changes throughout the cerebral cortex, hippocampus, amygdala and medial thalamus, with a different temporal progression, showing a complete recovery only after 3 days. Two hours after seizures, the apparent diffusion coefficient was decreased throughout the brain compared to control animals, and a further decrease was evident 24 h after seizures. This was followed by a complete recovery at 3 days post-seizures. Functional MRI was performed using regional cerebral blood volume (rCBV) maps. The rCBV was increased shortly after convulsions (2 h) in all structures investigated, with a significant return to baseline values in the parietal cortex and hippocampus, but not in the medial thalamic nuclei, 24 h after seizure onset. No rCBV alterations were detected 3 days after seizures. Electron microscopy of tissue samples of parietal neocortex and hippocampus revealed prominent astrocytic swelling 2 h post-convulsions which decreased thereafter gradually. In conclusion, this experiment reports for the first time structural and functional brain alterations, lasting several hours, in 4-aminopyridine-treated rats after seizure onset. MRI approach combined with histological and ultrastructural analysis provided a clarification of the mechanisms involved in the brain acute response to ictal activity.

Abstract: OBJECTIVE: We studied ob/ob and wild-type (WT) mice to characterize the adipose tissues depots and other visceral organs and to establish an experimental paradigm for in vivo phenotyping. RESEARCH METHODS AND PROCEDURES: An in vivo evaluation was conducted using magnetic resonance imaging and 1H-magnetic resonance spectroscopy (1H-MRS). We used T1-weighted images and three-dimensional spin echo T1-weighted images for the morphological analysis and 1H-MRS spectra on all body mass, as well as 1H-MRS spectra focalized on specific lipid depots [triglyceride (TG) depots] for a molecular analysis. RESULTS: In ob/ob mice, three-dimensional evaluation of the trunk revealed that approximately 64% of the volume consists of white adipose tissue, which is 72% subcutaneous and 28% visceral. In vivo 1H-MRS showed that 20.00 +/- 6.92% in the WT group and 58.67 +/- 6.65% in the ob/ob group of the total proton content is composed of TG protons. In in vivo-localized spectra of ob/ob mice, we found a polyunsaturation degree of 0.5247 in subcutaneous depots. In the liver, we observed that 48.7% of the proton signal is due to water, whereas in the WT group, the water signal amounted to 82.8% of the total proton signal. With the sequences used, the TG amount was not detectable in the brain or kidneys. DISCUSSION: The present study shows that several parameters can be obtained by in vivo examination of ob/ob mice by magnetic resonance imaging and 1H-MRS and that the accumulated white adipose tissue displays low polyunsaturation degree and low hydrolipidic ratio. Relevant anatomical alterations observed in urinary and digestive apparatuses should be considered when ob/ob mice are used in experimental paradigms.

Abstract: Temporal lobe epilepsy (TLE) is the most common and pharmacoresistant form of epilepsy. Problems that cause pharmacoresistance may include delayed therapy due to late consultation, especially in developing countries. Our study aimed at unraveling consequences of delayed drug treatment using a rat model of TLE. Following pilocarpine-induced status epilepticus interrupted after 4h, rats were continuously videorecorded for onset and recurrence of spontaneous convulsive seizures. The animals were then treated for 50 days with carbamazepine (CBZ; first-line drug in TLE and effective also in rats), starting at seizure onset (27.22+/-3.38 days after status epilepticus) or 50 days later, and compared with epileptic untreated rats and non-epileptic CBZ-treated ones. Convulsive seizure frequency and duration, and hippocampal cell changes were evaluated. In particular, parvalbumin-containing hippocampal interneurons, astrocytes and microglia were characterized with immunohistochemistry and quantitative analyses. Prompt administration of CBZ suppressed seizures; delayed treatment only decreased frequency of convulsive seizures, which were also relatively prolonged. In hippocampal regions, histopathological damage, parvalbumin immunoreactivity loss, and glial activation were very marked after delayed treatment, and were reduced only slightly compared to untreated epilepsy, but enhanced compared to early treatment. The data on high frequency and duration of convulsive seizures in late-therapy rats indicate that delayed CBZ administration caused a high degree of drug resistance. This condition was subserved by severe damage in the hippocampus, presumably consequent to long-term seizure recurrence. Overall the data indicate that the paradigm of delayed treatment of limbic epilepsy could provide a model of drug-refractory TLE with hippocampal sclerosis.

Abstract: This preliminary study describes magnetic resonance imaging (MRI) data on the effects of sub-chronic nicotine administration in rats. Nicotine 0.4 mg/kg s.c. free base was given once a day for 4 days to Wistar adult male rats. On day 5, anaesthetized subjects were observed using an MRI tomography system. Regional cerebral blood volume (rCBV) and transversal relaxation time (T2) MRI parameters were measured. Nicotine treatment increased T2 values, with a significant effect in the cingulate cortex. A trend to increase was also observed in the prefrontal cortex and nucleus accumbens. Similarly, the effect of nicotine on rCBV was a significant increase in values compared to saline treatment. Post hoc analysis showed a significant effect of nicotine in the prefrontal cortex, cingulate cortex, mediodorsal thalamus and lateral posterior thalamus. This study showed for the first time that sub-chronic nicotine administration can induce changes in MRI pattern which are (i) similar to human MRI studies, and (ii) common to those described for markers of neuronal metabolic activation in corticolimbic brain regions known to be involved in nicotine dependence.

Abstract: Seven human fetuses of crown/rump length corresponding to gestational ages ranging from the 12th to the 16th week were studied using a paradigm based on three-dimensional reconstruction of the brain obtained by magnetic resonance imaging (MRI). The aim of the study was to evaluate brain morphology in situ and to describe developmental dynamics during an important period of fetal morphogenesis. Three-dimensional MRI showed the increasing degree of maturation of the brains; fronto-occipital distance, bitemporal distance and occipital angle were examined in all the fetuses. The data were interpreted by correlation with the internal structure as visualized using high-spatial-resolution MRI, acquired using a 4.7-T field intensity magnet with a gradient power of 20 G cm(-1). The spatial resolution was sufficient for a detailed detection of five layers, and the contrast was optimized using sequences with different degrees of T1 and T2 weighting. Using the latter, it was possible to visualize the subplate and marginal zones. The cortical thickness was mapped on to the hemispheric surface, describing the thickness gradient from the insular cortex to the periphery of the hemispheres. The study demonstrates the utility of MRI for studying brain development. The method provides a quantitative profiling of the brain, which allows the calculation of important morphological parameters, and it provides informative regarding transient features of the developing brain.

Abstract: We analyzed modifications in transversal relaxation time (T2) and regional cerebral blood volume (rCBV) in two areas of the limbic system, i.e., olfactory bulb (OB) and amygdala (AMY), in pre-puberty and post-puberty female rats. The aim of this work was to extend the knowledge about physiological modifications of these MRI parameters at different developmental phases. No significant difference was observed in T2 values of the OB between the two groups (pre-puberty: T2 = 86.92 +/- 8.57 ms, post-puberty: T2 = 88.11 +/- 13.06 ms; mean +/- S.D.). On the contrary T2 values of the AMY were significantly different (P = 0.0001) between the two groups (pre-puberty 76.08 +/- 3.2, post-puberty 81.77 +/- 11.77 ms). rCBV values of OB were significantly different (P = 0.0025) between pre-puberty (0.38 +/- 0.12 a.u.) and post-puberty female rats (0.15 +/- 0.09 a.u.). A significant decrease in rCBV (P = 5.1 x 10(-13)) between pre-puberty and post-puberty females (pre-puberty: 0.36 +/- 0.12, post-puberty: 0.07 +/- 0.05 a.u.) was also observed in the AMY. These findings suggest that in the limbic system, microvascular plasticity parallels neuronal maturation and indicate the importance of an appropriate baseline study in experiments dealing with the limbic system performed at different time-points.

Abstract: Previous studies demonstrated that the spiny rat Proechimys guyannensis exhibits resistance to experimental epilepsy. Neural activation was studied in the Proechimys hippocampus, using Fos induction, within 24 h after pilocarpine-induced seizures; neurodegenerative events were investigated in parallel, using FluoroJade B histochemistry. These parameters were selected since pilocarpine-induced limbic epilepsy is known to elicit immediate early gene expression and cell loss in the hippocampus of seizure-prone laboratory rodents. At variance with matched experiments in Wistar rats, pilocarpine injection resulted in Proechimys in seizure episodes that, as previously reported, did not develop into status epilepticus. At 3 h and 8 h after seizure onset, Fos immunoreactivity filled the dentate gyrus of both rat species, and was quite marked in pyramidal cells of the Proechimys Ammon's horn. At 24 h, Fos immunoreactivity dropped in the Wistar hippocampus and persisted in Proechimys. At 8 h and 24 h, FluoroJade-stained neurons were very few in the Proechimys hippocampus, whereas they were abundant in that of Wistar rats. Double immunohistochemistry for Fos and parvalbumin, the protein expressed by fast-spiking hippocampal interneurons, indicated that Fos was induced up to 24 h in the vast majority of parvalbumin-containing cells of the Proechimys hippocampus, and in a minority of these cells in the Wistar hippocampus. The findings demonstrate that early postepileptic neurodegeneration is very limited in the Proechimys hippocampus, in which sustained Fos induction persists for several hours. The findings also indicate that Fos induction and persistence may not correlate with seizure intensity and may not be associated with neuronal death. Finally, the data implicate differential mechanisms of interneuron activity in anti-convulsant and pro-convulsant phenomena.

Abstract: In order to investigate epilepsy, that is one of the most common neurological disorders, in the last decades different animal models have been proposed. Prevention, diagnosis, treatment and basic knowledge have been improved by the mean of these models. Numerous animal models have been developed in epilepsy research, both for generalized and for simple/complex partial seizures. Animal models for generalized seizures include sensory (light, noise, movement, etc) or electrical stimulations and genetic models. Models for focal seizures include topical or systemic application of pro-convulsive compounds or electrical stimulation. Baboons, mice, rats, rabbits, and Fayoumi chicken have been extensively used in this regard. Since 1983, when magnetic resonance spectroscopy was used to evaluate for the first time in vivo alterations induced by status epilepticus in rabbit, an increasing interest for the neuroimaging perspective has led to new insights in the study of epileptic disorders. In the early 1990s experimental studies provided evidence for the feasibility of magnetic resonance imaging analysis and detection of tissue damage in kainic acid-induced epilepsy in rat. In the following years a wealth of data has been obtained by the mean of functional MRI and/or by diffusion-weighted images. The studies reported in the literature of the last decades indicate in vivo magnetic resonance of epilepsy model as valuable and extremely informative tool.

Abstract: The rat brain was investigated with structural and functional magnetic resonance imaging (MRI) 12 h after the arrest of pilocarpine-induced status epilepticus lasting 4 h. Histopathological data, obtained immediately after MRI analysis, were correlated with the images through careful evaluation of tissue shrinkage. Diffusion-weighted and T2-weighted imaging showed changes throughout the cerebral cortex, hippocampus, amygdala, and medial thalamus. However, only T2-weighted imaging, based on rapid acquisition relaxation-enhanced sequences, revealed in the cortex inhomogeneous hyperintensity that was highest in a band corresponding to layer V. Regional cerebral blood volume (rCBV) maps were generated using T2*-weighted gradient-echo images and an ultrasmall superparamagnetic iron oxide contrast agent. In the cortex, rCBV peaked in superficial and deep bands exhibiting a distribution complementary to the highest T2-weighted intensity. Selective rCBV increase was also documented in the hippocampus and subcortical structures. In tissue sections, alterations indicative of marked edema were found with Nissl staining in areas corresponding to the highest T2-weighted intensity. Degenerating neurons, revealed by FluoroJadeB histochemistry, were instead concentrated in tissue exhibiting hyperperfusion in rCBV maps, such as hippocampal subfields and dentate gyrus, cortical layers II/III and VI, and medial thalamus. The data indicate that:(i) T2-weighted imaging provides a sensitive tool to investigate edematous brain alterations that follow sustained seizures; (ii) rCBV maps reveal regional hyperperfusion; (iii) rCBV peaks in tissue exhibiting marked neurodegeneration, which may not be selectively revealed by structural MRI. The findings provide an interpretation of the brain response to sustained seizures revealed in vivo by different strategies of MRI analysis.

Abstract: This study was designed to evaluate the influence of age on the dynamic contrast-enhanced MRI of ischemic tissue. A well-established model of peripheral arterial insufficiency (i.e., the rat hindlimb ischemia after removal of femoral artery) in different age groups (i.e., young, presenescent, and senescent rats) was studied. The analysis of the MR signal demonstrated a marked accumulation of a contrast agent (Gd-DTPA) in the ischemic leg (ischemia-related enhancement, IRE). IRE was an age-related event: 4-month-old rats showed a strong IRE while 12-month-old rats and 20-month old rats showed a significantly reduced IRE in comparison to young animals. Histological analysis of the ischemic muscles revealed that there was no evidence of significant necrosis of the muscle tissue but only a weak interstitial fibrosis; CD31-immunostaining revealed a preserved microcirculatory bed.

Abstract: A brief survey of cortical development is presented, focusing on neuronal migration and its alterations. Corticogenesis is achieved through ordered temporospatial steps, via the formation of transient structures, and successive waves of cell proliferation and migration (followed by cell differentiation and maturation), and apoptotic cell death. The appearance of the proliferative ventricular zone and marginal zone, and of the superficial primordial plexiform layer, is followed by the formation of the prospective layer I, of the subplate, whose neurons are destined to die, and of the cortical plate that will give rise to layers II-VI. Cells arising in the ventricular zone migrate radially using radial glia as a scaffold, and are destined to form pyramidal cells. Cortical interneurons are mainly generated in the ganglionic eminence and migrate along axonal substrates following tangential routes. Disorders of this complex process lead to a wide range of alterations, and focal derangements of cortical organization have been grouped under the term focal cortical dysplasia (FCD). As the result of a neuropathological revision of FCD cases with intractable epilepsy, a novel classification comprising three subgroups of FCD has been introduced, and is supported by electroclinical and neuroimaging data, as well as by the postsurgical outcome of patients: i). architectural dysplasia, characterized by altered cortical lamination; ii). cytoarchitectural dysplasia, with the occurrence of giant neurons besides cortical dyslamination; iii). Taylor-type cortical dysplasia, in which altered cortical lamination is consistently associated with the occurrence of giant, dysmorphic and ectopic neurons, and frequently with the so-called balloon cells.

Abstract: It has been repeatedly reported that Fos is spontaneously induced in several brain structures, including the cerebral cortex, during wakefulness. To ascertain whether cortical interneurons are involved in this state-dependent oscillation of gene regulation, we combined Fos immunocytochemistry with immunostaining of either parvalbumin or calbindin, known markers of cortical interneurons. Immunopositive neurons were examined in the sensorimotor and cingulate cortex. In rats perfused in basal conditions, a minor proportion (around 8%) of Fos-immunoreactive neurons in the parietal cortex were also parvalbumin- or calbindin-immunoreactive; these double immunostained cells accounted for 13% of the parvalbumin- and 34% of the calbindin-labeled neurons. Colocalization of Fos with either calcium-binding protein was instead not observed in the cingulate cortex. In rats stimulated by novel environmental cues during the period of wakefulness preceding perfusion, Fos-positive neurons increased markedly relative to unstimulated animals, and involved the majority of the calbindin- or parvalbumin-labeled cell populations (60-75% and over 95%, respectively). In the neuronal populations in which Fos was induced by exposure to the enriched environment, the proportion of calbindin- and parvalbumin-labeled cells was larger than in the unstimulated cases, and the increment was statistically significant in the cingulate cortex. The results demonstrate that Fos induction occurring in the cortex during undisturbed wakefulness in a familiar environment involves a minor proportion of interneurons. Furthermore, the findings indicate that the addition of novel environmental stimuli results in an increase of Fos-expressing neurons whose recruitment, at least in the cingulate cortex, involves a higher proportion of interneurons than of projection neurons.

Abstract: In the P(50) gating or conditioning-testing paradigm in the rat, two identical click stimuli are presented with an inter-click interval of 500 ms. The reaction towards the second click, as measured with evoked potentials, is reduced in respect to that towards the first click; this phenomenon is called sensory gating. In the present experiments, the inter-click interval was varied systematically and auditory evoked potentials were measured. Sensory gating was found to occur only at intervals between 500 and 1000 ms, but not at longer intervals. Fos immunohistochemistry was then performed using two groups of rats exposed to double clicks: the inter-click interval was 500 ms in the experimental group and 2500 ms in the control group. Fos induction was analyzed in selected brain structures. In the auditory pathways, Fos-immunoreactive neurons were found in both groups of rats in the inferior colliculus and medial geniculate body. Fos-immunoreactive cells were also examined in the septum and hippocampus. In the ventral part of the lateral septal nucleus, the labeled neurons were significantly fewer in the experimental animals compared to the control group. Smaller and non-significant quantitative differences of Fos-positive neurons were documented in the medial septum and hippocampal CA1 region. These data point out a selective decrease in the lateral septum of Fos induced by auditory sensory gating, and suggest an involvement of this structure, and possibly of other parts of the septo-hippocampal system, in sensory gating mechanisms. The results might be relevant for theories on sensory gating deficits in schizophrenia.

Abstract: At variance with pilocarpine-induced epilepsy in the laboratory rat, pilocarpine administration to the tropical rodent Proechimys guyannensis (casiragua) elicited an acute seizure that did not develop in long-lasting status epilepticus and was not followed by spontaneous seizures up to 30 days, when the hippocampus was investigated in treated and control animals. Nissl staining revealed in Proechimys a highly developed hippocampus, with thick hippocampal commissures and continuity of the rostral dentate gyri at the midline. Immunohistochemistry was used to study calbindin, parvalbumin, calretinin, GABA, glutamic acid decarboxylase, and nitric oxide synthase expression. The latter was also investigated with NADPH-diaphorase histochemistry. Cell counts and densitometric evaluation with image analysis were performed. Differences, such as low calbindin immunoreactivity confined to some pyramidal cells, were found in the normal Proechimys hippocampus compared to the laboratory rat. In pilocarpine-treated casiraguas, stereological cell counts in Nissl-stained sections did not reveal significant neuronal loss in hippocampal subfields, where the examined markers exhibited instead striking changes. Calbindin was induced in pyramidal and granule cells and interneuron subsets. The number of parvalbumin- or nitric oxide synthase-containing interneurons and their staining intensity were significantly increased. Glutamic acid decarboxylase(67)-immunoreactive interneurons increased markedly in the hilus and decreased in the CA1 pyramidal layer. The number and staining intensity of calretinin-immunoreactive pyramidal cells and interneurons were significantly reduced.These findings provide the first description of the Proechimys hippocampus and reveal marked long-term variations in protein expression after an epileptic insult, which could reflect adaptive changes in functional hippocampal circuits implicated in resistance to limbic epilepsy.

Abstract: Camillo Golgi discovered, in 1898, the cell organelle that has been called, after him, "the Golgi apparatus" or "the Golgi complex." Because of the necessity of saving words in scientific literature, "the Golgi apparatus" is nowadays frequently referred to only as "the Golgi" or used in an adjectival form in combination with a variety of terms (e.g., Golgi vesicle, Golgi area, Golgi traffic, and so forth). We present here a search of the Medline database for the years 1967 through 1997, which demonstrates that the eponym has lost all connection with Golgi's personal identity. In addition, the search indicates that interest in the Golgi apparatus is steadily increasing, as evidenced in the scientific literature, and that Golgi's name is much more frequently used in association with the cell organelle than with any of the other scientific contributions of this scientist, including the Golgi impregnation of nerve cells.