Early onset of age-related changes on neural processing in rats.

Altered perceptual and emotional processing might bind impaired cognitive mechanisms during aging; however the nature of these sensory perception modifications is still unknown. In the present experiment we analyzed in rats, from early to mature life (2 to 11 months old), the response to unattended auditory evoked stimulation (Auditory evoked potential, AEP) and the power spectrum of spontaneous electroencephalogram (EEG), with the aim of unraveling the onset and target functional effects of aging. Somatosensory and cingulate cortex, mediodorsal thalamus and CA3 hippocampus were chosen for examination based on their involvement in sensory processing and age-related deficits. The main finding of this study is the early onset of age-related changes in adult rats as can be established with both AEP's and frequency analyses, and its diversity between brain regions during normal aging.

Forced mild physical training-induced effects on cognitive and locomotory behavior in old mice.

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.

Drug resistance and hippocampal damage after delayed treatment of pilocarpine-induced epilepsy in the rat.

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.

Structural and functional MRI following 4-aminopyridine-induced seizures: a comparative imaging and anatomical study.

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.

In vivo MRI in different models of experimental epilepsy.

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.

Magnetic resonance imaging of changes elicited by status epilepticus in the rat brain: diffusion-weighted and T2-weighted images, regional blood volume maps, and direct correlation with tissue and cell damage.

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.

The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes.

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.

Neural correlates of sensory gating in the rat: decreased Fos induction in the lateral septum.

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.

1898-1998: Camillo Golgi and "the Golgi": one hundred years of terminological clones.

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.