Reduced grey and white matter volumes in the temporal lobe of male patients with chronic schizophrenia

Magnetic resonance imaging (MRI) and tissue segmentation were used to quantify grey matter, white matter and cerebrospinal fluid (CSF) volumes in the brains of 32 males with chronic schizophrenia and 32 healthy males. Tissue volumes in the frontal, temporal, parietal, and occipital regions were measured separately. Males with schizophrenia had significant reductions of grey and white matter volumes in the temporal regions compared with controls. Patients also had significantly smaller white matter volumes in the cerebrum and increased CSF volumes in the frontal and the temporal regions as well as the cerebrum. The findings of the present study suggest that volumes of grey and white matter are reduced in the temporal region of males with chronic schizophrenia. The volume of white matter in the whole brain also appears to be reduced. Among the different brains regions, grey matter reduction was significant only in the temporal region. Received: 17 September 2001 / Accepted: 5 April 2002     

Cerebellar Glucose During Fasting and Acute Hyperglycemia in Nondiabetic Men and in Men with Type 1 Diabetes

In diabetic patients, proton magnetic resonance spectroscopy (¹H MRS) has revealed increased brain glucose concentration and metabolite alterations that indicate neuronal damage and glial cell activation. Cerebellum is known to be more resistant to hypoglycemia than cerebrum, but the effects of both chronic and acute hyperglycemia on the cerebellum are less well known. ¹H MRS was used to quantify brain glucose and metabolite levels in the cerebellum, cerebral cortex, cerebral white matter, and the thalamus of diabetic and nondiabetic men after an overnight fast and during a hyperglycemic normoinsulinemic clamp with blood glucose 12 mmol/l above baseline. Fasting glucose levels were twice as high in the cerebellum than in the cerebrum. During acute hyperglycemia, the cerebellar glucose concentration increased by 3.0 mmol/l, which equals that in the cortex, but is 35% more than in the thalamus and 173% more than in the white matter. Acute hyperglycemia also increased the cerebellar tissue water content by 10%. There were no differences between diabetic and nondiabetic participants. Notably, the patients with complication free type 1 diabetes showed brain metabolite alterations in the cerebral cortex and the white matter but not in the cerebellum. Our study suggests that diabetes does not alter glucose content or uptake in the cerebellum. The increase in tissue water during acute hyperglycemia may serve to protect the cerebellum from the potentially deleterious effects of the excess glucose.     

Vacuolization, incubation period and survival time analyses in three mouse genotypes injected stereotactically in three brain regions with the 22L scrapie strain

In previous studies we showed that C57BL mice injected stereotactically in the cerebellum with the 22L scrapie strain had a significantly shorter incubation period than those injected with the same agent in other brain regions. In mice injected in the cerebellum, vacuolization was limited to the cerebellum, medulla and mesencephalon, whereas injection into forebrain regions resulted in vacuolization in all brain regions. The studies suggested that the cerebellum had a selective vulnerability for 22L. In this study we examined the interaction between host genotype and selective vulnerability of specific brain regions. The mouse gene that has the most profound effect on pathogenesis, particularly incubation period, is termed Sinc (scrapie incubation). Groups of mice with three genotypes of Sinc (s7s7, p7p7 and their F1 cross, s7p7) were injected with 22L into the cerebral cortex, thalamus or cerebellum. Analysis of incubation periods showed that, regardless of the host genotype, the cerebellum injection group had a significantly shorter incubation period than groups injected in other regions. After cerebellum injection vacuolization was limited to the cerebellum, medulla and mesencephalon in all three host genotypes. The location of vacuoles within the cerebellum differed depending upon the host strain. Vacuolization developed almost exclusively in grey matter in s7s7 mice, mainly in white matter in p7p7 mice, and in both grey and white matter in F1 mice. These results demonstrate that the selective vulnerability of the cerebellum to induction of clinical disease by 22L does not depend on host genotype, but host genotype does affect lesion distribution within the cerebellum.     

Distribution of Thy-1 in human brain: Immunofluorescence and absorption analyses with a monoclonal antibody

A monoclonal antibody to human Thy-1 has been used to study the anatomical localization of Thy-1 in human brain and to quantitate the relative amounts of Thy-1 in different brain subregions. Quantitative absorption analyses using homogenates of carefully dissected brain subregions, together with an [¹²⁵I]anti-immunoglobulin binding assay using brain homogenate as target, established that Thy-1 was present in large amounts throughout human brain, but the grey matter of cerebrum (cortical grey matter, caudate nucleus, putamen and thalamus) had 5–10 times as much Thy-1 as white matter. Grey matter of cerebellum (cerebellar cortex and dentate nucleus) also had higher amounts of Thy-1 than white matter, but the total amount of Thy-1 in cerebellum was less than in the cerebrum. Immunofluorescence studies gave interesting results and demonstrated in particular: (a) the outlining of some neuronal cell bodies and their processes (particularly the Purkinje cells of the cerebellar cortex) by spots of fluorescence; (b) staining of what appeared to be cell bodies of satellite cells in areas of grey matter; (c) granular staining in grey but not white matter; (d) staining of what appeared to be fibre tracts in the basal ganglia and thalamus, the tracts appearing duller than the surrounding grey matter of the nuclei; (e) staining of only some fibres in sciatic nerve; and (f) absence of staining of the adrenal gland.     

Neuropathology of twitcher mice: examination by histochemistry,immunohistochemistry, lectin histochemistry and fourier transform infrared microspectroscopy

The twitcher mouse is an authentic animal model of globoid cell leukodystrophy, which is a genetic disease that affects the lysosomal enzyme galactocerebroside β-galactosidase. This enzyme deficiency causes one of its substrates, galactosylsphingosine (psychosine), to accumulate in myelin-forming cells, which eventually results in their death. In the central nervous system, the death of oligodendrocytes is thought to cause a series of secondary pathological changes. In this study, several techniques were utilized to examine the neuropathology of two different brain regions in the twitcher mouse—the hindbrain and the cerebrum. Neuropathological changes were as follows: (1) demyelination was detected in the hindbrain but not in the cerebrum, (2) a high density of periodic acid-Schiff-positive cells were detected in the hindbrain and to a lesser extent in the cerebrum, (3) astrocyte gliosis was pronounced in both the hindbrain and cerebrum, and (4) macrophages were abundant in both the hindbrain and the cerebrum. We found that Periodic acid-Schiff-positive cells, astrocyte gliosis and macrophage infiltration were present in white and gray matter regions of the cerebrum, while they were generally absent from the granule and molecular layers of the cerebellum. In addition to these studies, we utilized the technique of Fourier transform infrared (FT-IR) microspectroscopy to identify the in situ distribution of psychosine in the brains of twitcher mice. Evidence was obtained that indicates a large accumulation of psychosine in the hindbrain, and to a lesser extent in the white matter of the cerebrum in the twitcher mouse, but not the normal mouse. There was no evidence for the accumulation of psychosine in the molecular layer of the cerebellum from the twitcher or normal mouse. Our conclusions are as follows: (1) pathology is more advanced in the hindbrain compared to the cerebrum, which is likely due to the hindbrain becoming myelinated prior to the cerebrum, (2) demyelination is not necessary for the development of secondary pathological changes, (3) pathology is not limited to white matter in the cerebrum, (4) pathology is not present in all brain regions, i.e. the granule and molecular layers of the cerebellum are devoid of pathological changes, and (5) psychosine accumulates in both the cerebrum and hindbrain, but not in the molecular layer of the cerebellum in the twitcher mouse. This study demonstrates that FT-IR microspectroscopy can be used to correlate chemical changes to histopathological changes in brains from twitcher mice, which suggests that FT-IR microspectroscopy may be a useful tool for studies examining other brain diseases.     

Regional cerebral blood flow during hypercapnia in the anesthetized rabbit

These experiments were designed to test the hypothesis that increases in blood flow to the lower brainstem would be greater than forebrain regions during arterial hypercapnia. Total and regional cerebral blood flow (CBF) was measured via the tracer microsphere technique in seven anesthetized New Zealand white rabbits during normocapnia (arterial PCO2 congruent to 40 torr) and hypercapnia (arterial PCO2 congruent to 80 torr). During normocapnia average CBF was 0.77 ml/min/g, and regional measurements of blood flow indicated significantly greater flow to the cerebrum (0.86 ml/min/g) than either the medulla (0.52 ml/min/g) or the pons (0.49 ml/min/g). When arterial PCO2 was increased average CBF increased 113%, and a significant linear regression was calculated for arterial PCO2 vs CBF [CBF (ml/min/g) = 0.028 PCO2 (torr) - 0.502]. The distribution of blood flow within the brain was similar to normocapnia except that blood flow to the cerebellum was now greater than any other brain region (1.97 ml/min/g for the cerebellum compared to 1.66 ml/min/g for the cerebrum). Absolute increases in blood flow to the lower brainstem were equal to or less than other areas of the brain. We conclude that ponto-medullary blood flow does not increase disproportionate to other areas of the brain during hypercapnia, but some redistribution of CBF does occur in that cerebellar blood flow increased significantly more than the cerebrum, medulla, or pons.     

d-Amino-acid oxidase is confined to the lower brain stem and cerebellum in rat brain: regional differentiation of astrocytes

Based on enzymatic activity, the localization and the identification ofd-amino-acid oxidase-containing cells in rat whole brain was systematically studied in serial fixed sections. The oxidase activity was absent or scarce in the forebrain, was confined to the brain stem (midbrain, pons and medulla oblongata) and cerebellum, and its localization was extended to the spinal cord. In the brain stem the oxidase was mainly localized in the tegmentum, particularly in the reticular formation. The intense oxidase reactions were present in the red nucleus, oculomotor nucleus, trochlear nucleus, ventral nucleus of the lateral lemniscus, dorsal and ventral cochlear nuclei, vestibular nuclei, nuclei of posterior funiculus, nucleus of the spinal tract of the trigeminal nerve, lateral reticular nucleus, inferior olivary nucleus, and hypoglossal nucleus. In the cerebellum the activity in the cortex was much more intense than that in the medulla. In all the fields described above, the oxidase-containing cells were exclusively astrocytes including Bergmann glial cells, and neither neuronal components, endothelial cells, oligodendrocytes nor ependymal cells showed oxidase activity. These results indicated that the astrocytes regionally differentiated into two distinct types, one of which expressed oxidase in the midbrain, rhombencephalon and spinal cord, and the other which did not in the forebrain. The localization of the oxidase was inversely correlated with the distribution of freed-serine in mammalian brains (Nagata, Y., Horiike, K. and Maeda, T.,Brain Res., 634 (1994) 291–295). Based on the characteristic localization of the oxidase-containing astrocytes, we discussed the physiological role of the oxidase.     

Brain structural trajectories over the adult lifespan

The aim of this large-sample cross-sectional voxel-based morphometry (VBM) study of anatomical brain data was to investigate linear and nonlinear age-related trajectories of grey matter volume in the human brain during the adult lifespan. To date, there are only a few structural brain studies investigating local nonlinear aspects at the voxel level, i.e., without using anatomical ROIs as a priori hypothesis. Therefore, we analyzed 547 T1-weighted MR images of healthy adult brains with an age range of 19 to 86 years, including 161 scans of subjects with ages 60 and older. We found that the gray matter volume in some regions did not linearly decrease over time, but rather exhibited a delayed decline. Nonlinear age trajectories were observed in the medial temporal lobe regions, the basal ganglia, and parts of the cerebellum. Their trajectories indicated a preservation of grey matter volume during the early adult lifespan. Interestingly, we found nonlinear grey matter structural dynamics specifically in parts of the brain that have been extensively discussed in the context of learning and memory. We propose a hypothesis in relation to the functional role of these brain regions that may explain these results.     

The levels of adenosine and its metabolites in the guinea pig and rat brain during complete ischemia-in vivo study

Changes in levels of adenosine, inosine, hypoxanthine and ATP during complete ischemia after decapitation were determined in various areas of the guinea pig and rat brain using an HPLC method. These results were compared with levels in brains fixed by microwave irradiation. The levels of adenosine during 60 min of complete ischemia were extremely high and unevenly distributed while levels in the microwaved brains were very low and evenly distributed. The ratios of inosine plus hypoxanthine levels to adenosine which indicate the rate of metabolic degradation from adenosine into inosine and hypoxanthine, were also unevenly distributed during complete ischemia in the cerebellum, superior colliculus, cerebral cortex and hippocampus of the guinea pig and rat, and the highest ratio was observed in the cerebellum of the guinea pig and the superior colliculus of the rat. The activities of adenosine deaminase (ADA), one of the enzymes involved in adenosine metabolism, were measured in the four regions of the guinea pig. The ADA activities were unevenly distributed and the highest ADA activity was found in the cerebellum. These regional differences in ADA activities are in good agreement with the regional differences in the ratio of inosine plus hypoxanthine levels to adenosine during complete ischemia. Furthermore, the administration of EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride] (10 mg/kg, i.p.), an ADA inhibitor, caused a significant increase of adenosine and decrease of inosine formation in all four regions and a drastic effect on the cerebellum with high ADA activity compared with the other regions in the guinea pig brain. These results indicate that the changes in concentrations of adenosine and its metabolites (inosine and hypoxanthine) during complete ischemia depend on ADA activity in each brain region.     

Species diversity of neuronectin and cytotactin expression patterns in the vertebrate central nervous system

Two extracellular matrix proteins of brain tissue, neuronectin (NEC1) and cytotactin (CT), are disulfide-bonded multimers of M_r 180,000–250,000 subunits. The previously known distribution of these molecules is, however, very different. Human NEC1 is found throughout the white matter of rostral segments of the adult central nervous system (CNS) but not in rostral gray matter or in caudal CNS segments, including the cerebellum. In contrast, CT is absent or expressed at a low level in the adult chicken cerebrum but highly expressed in the cerebellum. Despite these differences in distribution, results obtained with antibodies that recognize NEC1 and CT in several vertebrate species indicate that these molecules are identical or at least closely related: (1) NEC1 antibodies recognize proteins affinity-purified with CT-binding proteoglycan; (2) proteins recognized by NEC1 and CT antibodies in cells constitutively expressing the molecules, cells in which expression is induced by growth factors and phorbol ester and cells treated with tunicamycin (to block glycosylation) are identical in subunit composition and mobility on SDS gels; (3) the removal of NEC1 from culture supernatants by immunoprecipitation removes all molecules reactive with CT antibodies and vice versa; (4) immunoblots of brain extracts with NEC1 and CT antibodies yield identical results. Having demonstrated the structural similarity between NEC1 and CT, we reexamined their distribution in the CNS. Surprisingly, the temporal and spatial distribution pattern of NEC1/CT varied greatly among species. Immunohistochemical and immunoblot experiments with adult human CNS tissues revealed significant levels of NEC1/CT in rostral but not caudal segments. In contrast, in cows and pigs the molecule is found throughout the CNS. Adult rat and mouse brains show regionally restricted expression of NEC1/CT in several areas of the cerebrum — distinct from those showing NEC1/CT in the human — and in the molecular layer of the cerebellum. Tests with fetal and newborn tissues revealed that CNS development in humans, cows and pigs is not accompanied by the marked decline in NEC1/CT levels or the changes in subunit composition found in the chicken CNS. The marked species diversity in temporospatial expression patterns suggests that intrinsic and/or extrinsic elements controlling the expression of NEC1/CT have diverged during vertebrate evolution.     

Brain ubiquitin is markedly elevated in Alzheimer disease.

Levels of ubiquitin, microtubule associated protein tau and tubulin were determined by immunoassays in homogenates of cerebrum and cerebellum of Alzheimer disease and aged control cases. Ubiquitin levels increased many fold in the cerebral cortex of Alzheimer disease cases and the increase correlated strongly with the degree of neurofibrillary changes in the tissue. The increase in ubiquitin was much less remarkable in the cerebral white matter. Cerebellum which is unaffected with neurofibrillary changes in Alzheimer disease had normal levels of ubiquitin both in gray matter and in white matter. There was an appreciable increase in abnormally phosphorylated tau in an Alzheimer disease brain with severe neurofibrillary degeneration, whereas the normal tau levels were increased only slightly. Tubulin was slightly decreased in the cerebral gray matter but not in the adjacent white matter. Marked increase in brain ubiquitin in Alzheimer disease suggests the role of ubiquitin in the pathobiology of Alzheimer disease.     

Oxidative stress, brain white matter damage andintrauterine asphyxia in fetal lambs

In order to examine the role of oxidative stress in asphyxia-induced perinatal braindamage, near-term fetal lambs were subjected to umbilical cord occlusion for approximately 60 min until fetal arterial pH diminished to less than 6.9 and base excess to less than −20 meq/l. Thelevels of superoxide, hydrogen peroxide, glutathione (GSH) and thiobarbiturate-reactivesubstances (TBARS) within brain grey and white matter were determined at 72 h to correlatewith morphological changes. Although the topography and extent of brain damage variedsomewhat from case to case, ranging from focal infarction in grey or white matter to subtle andpatchy alterations of white matter, the telencephalic white matter appeared to bear the brunt ofdamage as compared to other regions. The parietal white matter, in particular was often the seatof early pathological changes that could be seen in isolation. These white matter changes wereaccompanied by significant increases in hydrogen peroxide and TBARS levels as compared tothose in grey matter. In another set of experiments, 8 different brain regions were assayed forTBARS, GSH and superoxide dismutase (SOD). A highly significant rise in the levels of TBARSwas again noted in the parietal and frontal white matter. SOD levels were higher in the frontal andparietal white matter, basal ganglia and cerebellum. Cerebral cortical and hippocampal neuronswere relatively unaffected until accompanied by more severe damage to grey and white matter atother sites. These results suggest that the developing telencephalic white matter appears to bemost vulnerable to the effects of intrauterine fetal asphyxia and that oxidative stress may be amajor contributing factor in the pathogenesis of perinatal hypoxic–ischemic encephalopathy.     

Traumatic brain injury and grey matter concentration: a preliminary voxel based morphometry study

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown diffuse cerebral atrophy following traumatic brain injury. In the past, quantitative volumetric analysis of these changes was carried out by manually tracing specific regions of interest. In contrast, voxel based morphometry (VBM) is a fully automated technique that allows examination of the whole brain on a voxel by voxel basis. OBJECTIVE: To use VBM to evaluate changes in grey matter concentration following traumatic brain injury. METHODS: Nine patients with a history of traumatic brain injury (ranging from mild to severe) about one year previously were compared with nine age and sex matched healthy volunteers. T1 weighted three dimensional MRI images were acquired and then analysed with statistical parametric mapping software (SPM2). The patients with traumatic brain injury also completed cognitive testing to determine whether regional grey matter concentration correlated with a measure of attention and initial injury severity. RESULTS: Compared with controls, the brain injured patients had decreased grey matter concentration in multiple brain regions including frontal and temporal cortices, cingulate gyrus, subcortical grey matter, and the cerebellum. Decreased grey matter concentration correlated with lower scores on tests of attention and lower Glasgow coma scale scores. CONCLUSIONS: Using VBM, regions of decreased grey matter concentration were observed in subjects with traumatic brain injury compared with well matched controls. In the brain injured patients, there was a relation between grey matter concentration and attentional ability.     

Microinfarction as a result of hypertension in a primate model of cerebrovascular disease

Ten adult cynomolgus monkeys were studied as a non-human primate model of hypertensive cerebrovascular disease. Seven were made hypertensive by surgical coarctation of the aorta and three served as unoperated controls. After survival periods of 8–30 months, the brains were serially sectioned and surveyed for neuropathological changes. The most conspicuous change was minute areas of microinfarction in the white and gray matter. The lesions were of irregular shape with an average maximum diameter of less than 0.5 mm. They were slightly larger in the gray than in the white matter and appeared to be of different ages. Their area of predilection was the white matter of the forebrain, with smaller numbers in the cerebral cortex and scattered lesions elsewhere in the forebrain, brain stem and cerebellum. These microinfarcts did not correspond to usually described lesions in the human brain in hypertension or in other animal models of hypertensive cerebrovascular disease. We suggest that they represent an early change in the natural history of hypertensive neuropathology. Received: 1 September 1998 / Revised: 12 January 1999, 9 February 1999 / Accepted: 10 February 1999     

Disproportionate atrophy of cerebral white matter in chronic alcoholics

Morphometric analysis of postmortem brains from chronic ethyl alcohol abusers and controls was performed to determine the regional distribution and extent of atrophy in the cerebral hemispheres of alcoholics. This study was performed by digitizing photographs of coronal slices of the brains to compute the cross-sectional area of the cerebrum, cerebral cortex, subcortical nuclei, cerebral white matter, and the ventricular system at five standardized levels. Although the alcoholics and controls had similar demographic features and mean brain weights, brains from the alcoholic group showed mild but consistent atrophy of the cerebral cortex (2.5% to 4.2% reductions in cross-sectional area at all five levels), moderate atrophy of cerebral white matter (6.1% to 17.5% reductions), and enlargement of the ventricular system (31.8% to 71.9% increases). There were no differences in the sizes of subcortical nuclei. The absolute increase in the size of the ventricles in the alcoholic group was roughly equal to the amount of tissue lost in cerebral white matter, thereby representing hydrocephalus ex vacuo. The disproportionate loss of cerebral white matter relative to cerebral cortex suggests that a major neurotoxic effect of chronic alcohol intoxication in the central nervous system is axonal degeneration.     

Brain Volume Changes on Longitudinal Magnetic Resonance Imaging in Normal Older People

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.     

Ganglioside levels in hypoxic brains from neonatal and premature infants

In this study, 13 cases of newborn term-gestational infants and six cases of premature infants who died of hypoxia were selected for the determination of ganglioside levels in several regions of brains obtained at autopsy. Cases were divided into three groups according to the hypoxic interval and gestational age: Group A, six cases of newborn infants. The average time of hypoxia was 6.4 h. Group B, seven cases of newborn infants. The average time of hypoxia was about 71 h. Group C, six cases of premature infants. The average hypoxia time was 34.7 h. Frontal cortex, forebrain, hippocampus, and parahippocampal gyrus and cerebellum of each brain were examined. The method of Ladisch and Gillard (1985) was used to purify and quantify gangliosides. The results showed that total gangliosides decreased significantly in three regions of cerebral hemispheres of group B and in four brain regions of group C, as compared with group A (p<0.01). The amount of gangliosides in frontal cortex in group B was lower than in group C (p<0.01). The four major gangliosides (GM1, GD1a, GD1b, and GT1b) were all reduced in cerebral hemispheres of group B and C. In hypoxic brains, the percentage of gangliosides also showed some alterations. There was less GD1a in the cerebral hemispheres of group B and the frontal cortex of group C. The amount of GD1b was also less in the frontal cortex and forebrain of group B than in group A or C. The results suggest that severe hypoxia might cause decreases in brain gangliosides that correlate to the severity of brain damage.     

Cells of origin of several efferent pathways from the superior colliculus in Galago senegalensis.

Following upon previous studies on the lipid composition of the developing human brain, a further study is presented with the main object of tracing the chemical changes underlying the period of brain ‘growth spurt’. Gangliosides and plasmalogens were selected as approximate markers of synaptogenesis and myelination, respectively, and these lipids were compared in cerebrum and cerebellum to establish the time, if any, at which their rate of accretion increases in a significant way. In the forebrain the rate of increase in concentration of these lipids accelerated at about the 32nd week of gestational age. Although there were too few postnatal cases to draw very firm conclusions, it seemed that the ganglioside concentration levelled off at about two months postnatal age and that the plasmalogen concentration reached a plateau between the 4th and the 6th postnatal months. In the cerebellum the concentration of gangliosides was clearly lower than that in the forebrain until about one year of age, the maximum rate of increase occuring between the last weeks of gestation and the second postnatal month. The plasmalogen concentration was somewhat higher in the cerebellum than in the forebrain but the concentration profile was similar to that followed by the gangliosides. In clear contrast with the concentration profiles in the cerebrum, in the cerebellum both lipids apparently continued to increase up to the second postnatal year. A mainly perinatal period of vulnerability is suggested for the forebrain, and a more prolonged one (probably until the second year of life) for the cerebellum.     

Regional distribution of lead, zinc, iron and copper in suckling and adult rat brains

The flameless atomic absorption method was applied to reveal regional differences in heavy metals between suckling and adult rat brains. The lead concentration in the suckling brains were considerably different from those in the adult rats. The levels of lead concentration in the cerebrum and cerebellum of the normal suckling rats were 3–4 times higher than those of adult rats. Iron concentrations in the cerebrum of the suckling brains were approximately half those in the adult brains. Zinc and copper concentrations in medulla from the suckling rats were higher than those in the same region from the adult rats.     

Increased blood-brain barrier permeability in LP-BM5 infected mice is mediated by neuroexcitatory mechanisms.

Serum protein levels in LP-BM5 infected mouse brains were investigated to gain insight into the contribution of blood-brain barrier (BBB) patency to the pathogenesis of retroviral encephalopathy. Evans blue uptake by the forebrain and cerebellum was significantly increased between 8-12 weeks post inoculation. Immunohistochemistry revealed foci of albumin, transferrin, alpha(2)-macroglobulin and IgG transudation around blood vessels particularly in the cerebral cortex and cerebellar vermis. These leaks were often associated with astrocytosis and apoptotic cells. Unlike the other serum proteins, IgG immunoreactivity extended from the circumventricular organs and disseminated throughout the brain parenchyma, accumulating on the plasma membranes of hippocampal and cortical neurons. Consistent with the chronic elevation of free glutamate levels in LP-BM5 infected mice, the increase in Evans blue uptake into the forebrain was completely reversed following dizocilpine administration. Thus, the chronic increase in free glutamate levels in LP-BM5 infected mouse brain contributes to BBB disruption. Furthermore, the CNS accumulation of serum proteins, particularly IgG, observed in these mice may increase osmotic load, impair neuronal function, and cause white matter pallor. Administration of NMDA receptor antagonists may prove useful in managing BBB permeability in those neuropathologies, such as HIV-associated dementia/cognitive/motor complex, having a glutamatergic component.