Metallothionein-I induction by stress in specific brain areas

The distribution of metallothionein-I (MT) in several areas of the brain and its induction by immobilization stress has been studied in the rat. MT content was highest in hippocampus and midbrain and lowest in frontal cortex and pons plus medulla oblongata. Immobilization stress for 18 hours (which was accompanied by food and water deprivation) significantly increased MT levels in the frontal cortex, pons plus medulla oblongata and hypothalamus, but not in midbrain and hippocampus. The effect of stress on MT levels was specific as food and water deprivation along had no significant effect on MT levels in any of the brain areas studied. The effect of stress on MT levels was independent of changes in cytosolic Zn content; this was generally unaffected by stress or food and water deprivation but decreased in pons plus medulla oblongata from stressed rats. The results suggest that MT is induced more significantly in the brain areas that are usually involved in the response of animals to stress.     

Developmental Changes in the NGF Content in the Brain of Young,Growing, Low-Birth-Weight Rats

The NGF content in each region of the brain of four-week-old rats was ranked in the decreasing order of cerebral cortex, hippocampus, cerebellum, midbrain/diencephalon, and pons/medulla ob-longata, and the NGF concentration, in the decreasing order of hippocampus, cerebral cortex, cerebellum, midbrain/diencephalon, and pons/medulla oblongata in both AFD and SFD groups. The NGF content and concentration in the cerebral cortex were about the same value at each age between those in the AFD and SFD groups. Those in the hippocampus were a little higher in the SFD group than in the AFD group at the ages of three and four weeks, unlike those in the other regions, where the values for the cerebellum, midbrain/diencephalon and pons/medulla oblongata tended to be somewhat higher in the AFD group than in the SFD group. The NGF concentrations in the hippocampus and cerebral cortex increased with growth: the concentration in the hippocampus at four weeks of age was about 4-fold of that at one week in the AFD group and about 5.7-fold of that at one week in the SFD group; and likewise the concentration in the cerebral cortex at four weeks of age was about 5.3-fold in the AFD group and about 7-fold in the SFD group. The NGF concentrations in the cerebellum decreased, and those in midbrain/diencephalon and pons/medulla oblongata hardly changed with growth in either AFD or SFD group. From these results NGF may have stronger implications for the neuronal growth in the hippocampus compared with those in the lower brain regions of the SFD rats.     

Short latency somatosensory evoked potentials recorded around the human upper brain-stem

We analyzed the intracranial spatiotermporal distributions of the N18 component of short median nerve somatosensosry evoked potentials (SSEPs) in 3 patients with epilepsy. In these patients, depth electrodes were implanted bilaterally into the frontal and temporal lobes, with targets including the amygdala and hippocampus; the latter two targets are close to the upper pons and midbrain.In this study N18 was divided into the initial negative peak (N18a) and the following prolonged negativity (N18b). Mapping around the upper pons and midbrain showed that: (1) the amplitude of the first negativity, which coincided with scalp N18a, was larger contralateral to the side of stimulation, but showed no polarity change around the upper brain-stem; and (2) the second negativity, which was similar to scalp N18b, did show an amplitude difference or a polarity change. This wave appeared to reflect a positive-negative dipole directed in a dorso-ventral as well as dorso-lateral direction from the midbrain, where positivity arises from the dorsum of the midbrain, contralateral to the side of the stimulation.Recordings from depth electrode derivations oriented in a caudo-rostral direction suggest that N18a and N18b may in part reflect neural activity originating from the upper pons to midbrain region which projects to the rostral subcortical white matter of the frontal lobe as stationary peaks.     

Regional Development of Glutamate Dehydrogenase in the at Brain

The development of glutamate dehydrogenase enzyme activity in rat brain regions has been followed from the late foetal stage to the adult and through to the aged (greater than 2 years) adult. In the adult brain the enzyme activity was greatest in the medulla oblongata and pons greater than midbrain = hypothalamus greater than cerebellum = striatum = cortex. In the aged adult brain, glutamate dehydrogenase activity was significantly lower in the medulla oblongata and pons when compared to the 90-day-old adult value, but not in other regions. The enzyme-specific activity of nonsynaptic (free) mitochondria purified from the medulla oblongata and pons of 90-day-old animals was about twice that of mitochondria purified from the striatum and the cortex. The specific activity of the enzyme in synaptic mitochondria purified from the above three brain regions, however, remained almost constant.     

Origin and distribution of brain-stem somatosensory evoked potentials in humans

The distribution of somatosensory evoked potentials (SEPs) recorded from the brain-stem surface was studied to investigate their generator sources in 14 patients during surgical exploration of the posterior fossa. Two distinct SEPs of different morphologies and electrical orientation were obtained by median nerve stimulation. A small positive-large negative-late prolonged positive wave was recorded from the cuneate nucleus and its vicinity. There was a phase-reversal between the cuneate nucleus and the ventral surface of the medulla, depicting a dipole for dorso-ventral organization. From the pons and midbrain, triphasic waves with predominant negativity were obtained. This type of SEP had identical wave forms between dorsal, lateral and ventral surface of the pons and midbrain. It showed an increase in negative peak latency as the recording sites moved rostrally, suggesting an ascending axial orientation. In a patient with pontine hemorrhage, the killed end potential, a large monophasic positive potential was obtained from the lesion. This potential occurs when an impulse approaches but never passes beyond the recording electrode. Therefore, the triphasic SEP from the pons and midbrain reflects an axonal potential generated in the medial lemniscal pathway.     

Reappearance of brain-stem auditory evoked potentials after surgical treatment of a brain-stem hemorrhage: contributions to the question of wave generation

We report on a patient suffering a spontaneous hemorrhage primarily located in the right brain-stem; surgical correction of this led to a substantial improvement in clinical deficits. Brain-stem auditory evoked potentials (BAEPs) were recorded on postoperative days 18, 30, 55 and 205. Waves II through V were initially undetectable on stimulation of the damaged side, whereas the absence of peak V was the only abnormality seen on left-side stimulation. With the regression of the right lower mid-pontine deficits, the right waves gradually reappeared and normalized progressively. On the last recording, only a left wave V abnormality persisted. At that time, the patient had a moderate left hemisyndrome due to a circumscribed right upper pontine-midbrain lesion. Therefore, it can be suggested that the first 4 waves of BAEPs mainly originate in the ipsilateral pons, and the Vth in the contralateral higher regions.     

Origin of scalp far-field N18 of SSEPs in response to median nerve stimulation

To identify the origin of scalp-recorded far-field negativity of short-latency somatosensory evoked potentials to median nerve stimulation (designated N18), direct records were made from the thalamus and ventricular system during 4 stereotaxic and 3 posterior fossa operations.In the thalamus a negative potential with almost the same latency as the scalp N18 was restricted to the Vim nucleus, but there was a large positive potential in the VC nucleus and medial lemniscus. Vim negativity increased in amplitude when high frequency stimulation was given to the median nerve, indicative of a facilitation effect. In contrast, the amplitude of scalp N18 decreased at high frequency stimulus.Direct recordings made through the medulla oblongata to the mid-brain showed a negative potential with gradually increasing latency. Above the upper pons, there was stationary negativity with no latency shift. The similarity between this negative potential and N18 is shown by their having the same latency and same response to the amplitude reduction and latency prolongation produced by high frequency stimulus.Our data suggest that scalp N18 comes from brain-stem activity between the upper pons and the mid-brain rather than from the thalamus.     

Tissue specificity of calspermin: a heat-stable Mr 32,000 calmodulin-binding protein

We previously reported that rat testis and porcine testis contain a physicochemically indistinguishable Mr 32,000 calmodulin-binding protein, which we named "calspermin." In this study, antiserum against calspermin from porcine testis was raised in a rabbit, and a radioimmunoassay was developed. The antiserum reacted with calspermin from porcine testis but possessed little cross-reactivity against calspermin from rat testis. Among various porcine tissues, this protein was found primarily in testis, sperm, and brain. Its concentration in the cytosol was higher than that in the particular fraction in testis, but the reverse was found in brain. In brain, its concentration was highest in gray matter of cortex and in cerebellum, and became lower in tectum, white matter of cortex, hypothalamus, midbrain, and pons, in this order, and was nondetectable in medulla oblongata.     

Pathology of wave III of brainstem auditory evoked potentials (BAEPs).

In a group of 195 consecutively examined patients with brainstem neurological symptomatology parameters of the wave III BAEPs were pathological in 20 patients. In 70% of them the clinical symptomatology and/or the cranial computed tomography examination results pointed to a lesion at the level of pontomedullary junction and lower pons Varoli where according to the recent opinion the possible generators of this BAEP wave are situated (superior olivary complex, nuclei cochleares, corpus trapezoideum). These results support the supposed localization of possible generators of the wave III BAEPs.     

Brain adrenoreceptors in rats with inherited arterial hypertension due to emotional stress

For the study of genetic and physiological mechanisms of inherited stress-sensitive arterial hypertension, specific binding of ligands of alpha 1-, alpha 2- and beta-adrenoceptors was measured in 2 strains of rats: Wistar normotensive and ISSAH rats (rats with inherited stress-sensitive arterial hypertension). The maximal binding sites (Bmax) and apparent dissociation constants (Kd) were studied with the alpha 1-adrenergic antagonist 3H-prazosin, alpha 2-adrenergic agonist 3H-clonidine and 3H-dihydroalprenolol, a beta 1-receptor antagonist. Four brain regions were investigated: frontal cortex, hypothalamus, pons and medulla oblongata. In comparison with normotensive controls, hypertensive rats had significantly greater density of the alpha 1-adrenoceptors in the medulla oblongata. However, the number of hypothalamic alpha 1-adrenoceptors was significantly reduced in these animals. The same significantly lower alpha 2-adrenoreceptor density was found in the hypothalamus and the pons, and lower, beta-adrenoceptors density in the medulla oblongata. It was concluded that brain adrenoceptors are involved in the mechanisms of development of inherited stress-sensitive hypertensive syndrome.     

Analysis of translesion replication across an abasic site by DNA polymerase IV of Escherichia coli

Unrepaired replication-blocking DNA lesions are bypassed by specialized DNA polymerases, members of the Y super-family. In Escherichia coli the major lesion bypass DNA polymerase is pol V, whereas the function of its homologue, pol IV, is not fully understood. In vivo analysis showed that pol V has a major role in bypass across an abasic site analog, with little or no involvement of pol IV. This can result from the inability of pol IV to bypass the abasic site, or from in vivo regulation of its activity. In vitro analysis revealed that purified pol IV, in the presence of the beta subunit DNA sliding clamp, and the gamma complex clamp loader, bypassed a synthetic abasic site with very high efficiency, reaching 73% in 2 min. Bypass was observed also in the absence of the processivity proteins, albeit at a 10- to 20-fold lower rate. DNA sequence analysis revealed that pol IV skips over the abasic site, producing primarily small deletions. The RecA protein inhibited bypass by pol IV, but this inhibition was alleviated by single-strand binding protein (SSB). The fact that the in vitro bypass ability of pol IV is not manifested under in vivo conditions suggests the presence of a regulatory factor, which might be involved in controlling the access of the bypass polymerases to the damaged site in DNA.     

Anatomical aspects of the arteria inferior posterior cerebelli for posterior fossa surgery]

As the arteria inferior posterior cerebelli sometimes causes surprises of grave consequence at surgical approaches, its origin and course had to be described in detail. For this aim, we especially considered the local relationships of this artery with the medulla oblongata and the cranial nerves of the posterior fossa. Branches of the a. inferior posterior cerebelli supplying the medulla oblongata have been noticed in relation to the arterial supply of the medulla oblongata by corresponding vessels and the aa. spinales lateralis and posterior with special reference to all the possible collateralizations.     

Pregnancy close to the edge: an immunosuppressive infiltrate in the chorionic plate of placentas from uncomplicated egg cell donation

In pregnancies achieved after egg donation (ED) tolerance towards a completely allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still unknown. A distinct lesion not described previously in the literature, was repeatedly found in the chorionic plate in a substantial portion of placentas from ED pregnancies, but never in placentas from normal term pregnancies. The aim of this study was to assess its origin and its cellular composition. The relation between the lesion, the clinical and histological parameters were assessed. In addition we investigated the relation with the number of HLA-mismatches and KIR genotype of mother and child.In ten out of twenty-six (38.5%) placentas from ED pregnancies an inflammatory lesion was present in the chorionic plate. A significantly lower incidence of pre-eclampsia was found in the group with the lesion; 0% versus 45.5%. A significant relation was found between this lesion and the presence of intervillositis, chronic deciduitis, presence of plasma cells and fibrin deposition in the decidua. Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the majority of cells present in the lesion are of maternal origin. The expression of the macrophage marker CD14+ and of the type 2 macrophage (M2) marker CD163+ was significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was significantly higher in cases with a lesion compared to the group without the lesion. In conclusion, a striking relationship was observed between the presence of a not previously described inflammatory lesion in the chorionic plate and the absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly maternal cells with a higher expression of the macrophage marker CD14+ and the M2 marker CD163+. These findings suggest a protective immune mechanism which might contribute to the prevention of severe clinical complications like pre-eclampsia.     

Anterior spinal arteries. Origin and distribution in man

This study was designed to extend our present knowledge of the origin and distribution of anterior spinal arteries and was carried our using 31 human cadavers with arterial injections of natural latex. The conclusions reached are that there are always one or two anterior spinal arteries (right or left), which proceed from the intracranial segment of the vertebral arteries. These arteries have a descending course, with distribution into the ventral face of the medulla oblongata and the first cervical segments of the medulla spinalis. In cases where there are two anterior spinal arteries, they anastomose with each other to form the common, unpaired and median anterior spinal artery. The different observed locations of the origins of anterior spinal arteries may be systematised into three types. Each of these types has differential characteristics: bilateral origin (type I; 77.4%), unilateral origin (type II; 9.7%) and origin in an intervertebral transversal anastomosis (type III; 12.9%). We do however subdivide the bilateral origin group, according to the calibre of the arteries, into the subtypes 'balanced' (type Ia; 22.6%), 'right dominated' (type Ib; 32.2%) and 'left dominated' (type Ic; 22.6%). The collaterals of the anterior spinal arteries which distribute into the ventral face of the medulla oblongata are described.     

Afferent projections from the brainstem to the area hypothalamica dorsalis: a horseradish peroxidase study in the cat

Experiments using the retrograde transport of horseradish peroxidase were performed in order to identify the cells of origin the ascending projections from different brainstem regions to the area hypothalamica dorsalis (aHd) in the cat. The afferent inputs to this area originate mainly from the midbrain and medulla oblongata regions. The main afferent source of the area hypothalamica dorsalis arises from the substantia grisea centralis, where a large number of labeled cells were observed bilaterally, although more abundant on the ipsilateral side. Substantial afferents reach the aHd from the nuclei vestibularis medialis and inferior and the formatio reticularis mesencephali. A modest number of peroxidase-labeled neurons were observed in the nuclei ruber, interpeduncularis, substantia nigra, reticularis gigantocellularis, vestibularis lateralis, cuneatus and gracilis. From the pons, the nucleus raphe magnus sends a weak projection to the aHd. These anatomical data suggest that such area could be involved in visceral, sexual, nociceptive somatosensorial, sleep-waking and motor mechanisms.     

Effect of ethanol on cyclic AMP levels in the rat brain

Ethanol decreased in a dose-dependent manner the cyclic AMP level in the rat brain and separation of the brain into several parts showed that this decrease was limited to the cerebellum. High doses of ethanol (4–6 g/kg) blocked the rise of cyclic AMP levels induced by decapitation in all brain areas studied. Pentobarbital treatment which produced central depression similar to that caused by a high dose of ethanol, also decreased the cyclic AMP level in the cerebellum but it prevented the postdecapitation rise only in the pons and medulla oblongata. Lower doses of ethanol (1–2 g/kg) enhanced the decapitation-induced rise of cyclic AMP levels in the pons and medulla oblongata.     

Cellular and regional localization of the neurospecific antigen 10-40-4 in the human brain

Cellular and regional localization of neurospecific protein 10-40-4 in human brain was studied by immunofluorescent staining and immunoenzymatic assay. Intense fluorescence of perikaryons of the medulla oblongata, thalamus and pons neurons was demonstrated. The same structures showed the maximal concentration of the protein (15-18% of water-soluble proteins). In the cortex of the hemispheres, in the cerebellum and hypothalamus the fluorescence intensity was not different from the background level. The concentration of the protein in these structures was minimal (1-4% of water-soluble proteins).     

Permanent alterations of spinal cord reflexes following nerve lesion in newborn rats

Sciatic nerve lesion in newborn rats is known to cause degeneration of a large number of axotomized motoneurones and spinal ganglion cells. Some of the surviving motoneurones exhibit abnormal firing properties and the projection pattern of central terminals of sensory neurones is altered. We report here on long-term changes in spinal cord reflexes in adult rats following neonatal nerve crush. In acutely spinalized and anaesthetized adult rats 4-6 months old in which the sciatic nerve had been crushed on one side at birth, the tibial nerve, common peroneal nerve or sural nerve were stimulated on the reinnervated and control side and reflex responses were recorded from the L5 ventral spinal roots. Ventral root responses (VRRs) to tibial and peroneal nerve stimulation on the side of the nerve lesion were significantly smaller in amplitude representing only about 15% of the mean amplitude of VRRs on the control side. The calculated central delay of the first, presumably monosynaptic component of the VRR potential was 1.6 ms on the control side while the earliest VRR wave on the side of the nerve lesion appeared after a mean central latency of 4.0 ms that seems too long to be of monosynaptic origin. These results suggest that neonatal sciatic nerve injury markedly alters the physiological properties and synaptic connectivity in spinal cord neurones and causes a marked depression of spinal cord responses to peripheral nerve stimulation.     

Effects of acute and chronic toluene inhalation on behavior and (3H)-serotonin binding in rat

Toluene inhalation (0.7 % in air) induced in rats abnormal neurological states resembling the serotonin syndrome, such as hindlimb abduction, resting tremor and head weaving. The frequency and intensity of these responses were unchanged after two weeks of exposure (0.7 % in air, 15 min/day for 14 days), indicating an absence of tolerance development. An examination of specific serotonin (³H-5HT) binding to crude synaptic membranes prepared from brains of rats subjected to acute and chronic toluene exposure revealed that while no changes in either apparent Kd or apparent Bmax occured in acutely exposed animals, in chronically treated animals specific (³H)-5HT binding decreased in hippocampus and pons + medulla oblongata. These results indicate that serotonergic mechanisms may play a role in some of the effects of toluene inhalation in rats, but cannot explain the absence of tolerance development after chronic exposure to toluene.