Endopiriform nucleus connectivities: the implications for epileptogenesis and epilepsy

Several anterograde and retrograde tracing studies have provided detailed information on the afferent and efferent projections as well as the intrinsic connectivities of the endopiriform nucleus (EN). Here, we summarise EN connectional data and the principles of their organisation and discuss the role they may play in the development and spread of epileptic seizures

Reduced level of synapsin I protein in the rat striatum after intraventricular administration of proteasome inhibitors: preliminary studies

Background: We have recently described changes present in nigrostriatal terminals after intraperitoneal administration of MG-132 and changes that occur in the walls of the rat lateral ventricle after intraventricular administration of MG-132, lactacystin and epoxomicin — different classes of proteasome inhibitors. Substances that inhibit ubiquitin-proteasome system (UPS) activity, are intensively studied due to their potential role as novel therapeutic strategies in the treatment of cancer and ischaemia-reperfusion injury in the brain. The aim of this study is to determine the influence of intraventricular administration of MG-132, lactacystin and epoxomicin on the level in the rat striatum synapsin I — one of the most prominent neuron-specific phosphoproteins in the brain. Materials and methods and Results: Two weeks after administration of studied proteasome inhibitors, substantial reduction (up to 80%) of synapsin I was ob­served in the rat striatum. Because neurons, and especially dopaminergic ones, are sensitive to the depletion of proteasome function, we assume that observed synapsin I decrease may reflect changes in population of striatal neurons and/or nigrostriatal terminals. Conclusions: Understanding of cellular mechanisms standing behind our findings needs further studies, and could provide valuable contribution to the discussion on the mechanisms linking UPS inhibition and survival of neurons.

Minocycline but not valproic acid influence the density of NogoA-immunoreactive neurons in the hilus of the dentate gyrus of the rats subjected to intracerebral haematoma

Intracerebral haemorrhage is a devastating neurological disease with high mortality rate and poor prognosis. The most prominent manifestation of the disease arethe movement disorders, but many patients also suffer from cognitive impairment. Taking into account vulnerability of the neurons located within the hilus of the dentate gyrus (HDG) to many brain insults we decided to study the effectof experimentally induced intracerebral haematoma on density of neurons expressing NogoA protein in HDG. In addition, we studied how administration of valproic acid and minocycline, the two drugs generally believed to be neuroprotective agents, influences the density of these neurons. Our study revealed that 4 weeks after intracerebral haematoma induction, minocycline and valproic acid treatment increased the densities of NogoA-ir neurons in the hilus of contralateral dentate gyrus once the data were compared to ipsilateral hemispheres within the same group. The analysis of contralateral hemisphere data, however, revealed increased densities of NogoA-positive neurons in haematoma and valproic acidtreated animals when compared to contralateral hemispheres of control animals.The administration of minocycline was, however, able to alleviate this increase.These changes may influence the haematoma-induced reorganisation of neuronal circuitries in the dentate gyrus

The influence of acute and chronic open-field exposure on the hippocampal formation: an immunohistochemical study

The hippocampus plays a role in new learning, memory and emotion and is a component of the neuroanatomical stress circuit. The structure is involved in terminating hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress and attenuates stress responses by shutting off this axis. The immunoreactivity (-ir) of c-Fos, NGF and its receptor TrkA following acute and chronic open-field stress were studied in CA1-CA3 and the DG of the hippocampus. The material consisted of 21 male adult rats divided into three groups: nonstressed (control) animals and rats exposed to acute (15 min once) and chronic (15 min daily for 21 days) aversive stimulation (open-field exposure). The brains were stained with use of immunohistochemical methods for c-Fos, NGF or TrkA. In the animals exposed to acute open-field stress the number of c-Fos-, TrkAand NGF-ir cells was higher in all the structures studied than in the control animals. However they were differentiated only in c-Fos immunoreactivity. In the rats exposed to chronic open-field stress the number of c-Fos-ir cells in the structures of the hippocampal formation studied was smaller than in rats exposed to acute stress and was comparable to that in the control group. No differences were observed between the groups exposed to acute and chronic stress in the number of TrkA-ir cells in the structures under investigation. The number of NGF-ir neurons in CA1 and CA2 was lower after exposure to chronic than after exposure to acute stress but was still higher than that in the control group. Our findings indicate that neurons of CA1-CA3 and the DG are engaged in the stress response after acute as well as chronic open-field exposure. This is probably related to the important role of the hippocampus in processing new spatial information as well as in the habituation processes, although these appear to have different mechanisms

Analysis of calretinin immunoreactivity in the rat piriform cortex after open field stress during postnatal maturation

In our study we used c-Fos protein to identify whether cells containing calretinin (CR) in the rat piriform cortex are engaged in the response to stress stimulation and to find out how this expression changes during maturation (PC). The material consisted of Wistar strain rats of between 0 and 120 days of age divided into 9 groups. Each group consisted of 5 experimental and 3 control rats. Animals from the experimental groups were exposed to the open field test throughout 10 minutes. The control animals were kept in a home cage. In all age-related control rats weak c-Fos immunoreactivity was observed. Our results showed that cells containing c-Fos following an acute open field test were observed predominantly in layers II and III of the PC just after birth. Their number then increased and stabilised on P30. We had already observed immature CR-ir cells at birth. In the 4th week of life these neurons achieved maturity. Their number increased to P90 and decreased in older animals. CR-ir neurons were localised mainly in layer II and to a lesser degree in layers III and I of the PC. Double immunostaining c-Fos/CR revealed that the level of co-localisation was low. Only small differences were observed between the anterior and posterior parts of the PC. In the anterior part a higher number of CR-ir neurons was found. The difference in the level of co-localisation between the anterior and posterior parts was age-related and differentiated. Our results may suggest that during maturation CR-ir neurons of the piriform cortex are not the main population engaged in response to the open field test

Pyruvate dehydrogenase deficiency: morphological and metabolic effects, creation of animal model to search for curative treatment

The main source of energy for brain and other organs is glucose. To obtain energy for all tissue, glucose has to come through glycolysis; then as pyruvate it is converted to acetyl-CoA by pyruvate dehydrogenase complex (PDC) and finally enters citric acid cycle. What happens when one of these stages become disturb? Mutation in genes encoding subunits of PDC leads to pyruvate dehydrogenase deficiency. Abnormalities in PDC activity result in severe metabolic and brain malformations. For better understanding the development and mechanism of pyruvate dehydrogenase deficiency the murine model of this disease has been created. Studies on a murine model showed similar malformation in brain structures as in the patients suffered from pyruvate dehydrogenase deficiency such as reduced neuronal density, heterotopias of grey matter, reduced size of corpus callosum and pyramids. There is still no effective cure for PDC-deficiency. Promising therapy seemed to be ketogenic diet, which substitutes glucose to ketone bodies as a source of energy. Studies have shown that ketogenic diet decreases lactic acidosis and inhibits brain malformations, but not the mortality in early childhood. The newest reports say that phenylbutyrate increases the level of PDC in the brain, because it reduces the level of inactive form of PDH. Experiments on human fibroblast and zebra fish PDC-deficiency model showed that phenylbutyrate is promising cure to PDC-deficiency. This review summarizes the most important findings on the metabolic and morphological effects of PDC-deficiency and research for treatment therapy

Distribution of neuronal nitric oxide synthase (nNOS)-immunoreactive elements in the rabbit piriform cortex

The piriform cortex (PC), the primary olfactory cortex, is involved in the processes of learning and stress response and possibly plays an important role in epileptogenic activity. The results of several recent studies suggest that those PC neurons that contain neuronal nitric oxide synthase (nNOS) may play a key role during spatial learning and in the modulation of initiation, propagation and generalisation of seizures in various experimental models and may influence neuronal vulnerability after epileptic insults. The aim of this study was to characterise the pattern of distribution and morphology of nNOS-immunoreactive elements in PC of the adult rabbit. The co-localisation of nNOS and calretinin (CR) was also studied. The pattern of nNOS-ir within the rabbit PC is similar to that described previously in other mammals. The morphology of nNOS-ir elements, namely varicose fibres and Cajal-Retzius cells, suggest that NO has an important influence on PC function. Surprisingly, in the rabbit PC nNOS-ir elements show a very low level of co-localisation with CR-ir

Organisation of the dopamine neuronal subsets within midbrain of the feathertail glider (Acrobates pygmaeus, Acrobatidae, Marsupialia)

The Marsupial feathertail glider has a unique set of morphological, anatomical and behavioural features that make it a promising model for study of primate evolution. Among them it has many locomotor adaptations to arboreal life, such as diagonal gait of movements, gliding, fast climbing and running along branches. These ecological and behavioural specialisations could result in differences in anatomy of the brain systems involved in their integration. It is well acknowledged that dopaminergic neurons are involved in motor control, motivation and cognition. Due to the fact that there are no data on morphological organisation of dopaminergic system in the midbrain of this species, we decided to investigate it using immunohistochemical and quantitative methods. Our study showed that the general distribution and characteristics of the dopaminergic cells within midbrain nuclei of the pygmy acrobat is similar to that in other species, but it lack the substantia nigra compact part — ventral tier and “tail” of the substantia nigra subnuclei. This study provides the first description of the dopaminergic cells and nuclei in the midbrain of the feathertail glider and we hope it will start interest in the neurobiology of this species

The technique of inhalation anaethesia in experimental investigation in the rat

The rat is the most frequently used animal in scientific inquiry conducted for the purpose of advancing basic knowledge that may lead to an improvement in the results of treatment. Understanding of the pharmacological properties of inhalation anaesthetics, in combination with monitoring of their concentration in the inspired and end-tidal gas, together provide safe and precise control of the depth of the anaesthesia. However, accurate application of the inhalation method of anaesthesia requires special equipment for the delivery and effective scavenging of inhalation anaesthetics

The pathophysiology of intracerebral haemorrhage

Spontaneous intracerebral haemorrhage carries a high mortality rate and treatment of the disease raises more questions then answers. Mass effect, ischaemia and toxicity of blood components are responsible for brain tissue damage. Initially occurring disturbances of cerebral blood flow have a temporary character and do not play a key role in the pathology of intracerebral haematoma. Oedema formatting in the 24–48 hours after intracerebral bleeding is the result of multidirectional processes. The pathological mechanism that underlines it is the function of activation of systemic complement and cascade of coagulation. In the light of these findings, further clinical and experimental investigations should be focused on these factors