Immunocytochemical investigation on dysplastic human tissue from epileptic patients

In this report we describe three patients with developmental cortical abnormalities (generally referred as cortical dysplasia), revealed by MRI and operated on for intractable epilepsy. Tissue, removed for strictly therapeutic reasons, was defined as the epileptogenic area by electroclinical data and stereo EEG (SEEG) recordings. Tissue samples were processed initially for histology, and selected sections were further processed for immunocytochemical investigation in order to determine whether the region of cortical dysplasia was co-extensive with the epileptogenic area. In two patients with nodular heterotopia, disorganized aggregates of neurons (as revealed by neuronal cytoskeletal markers) were found within the nodules. Both pyramidal and local circuit neurons were present in the nodules, but no reactive gliosis was present. When nodules reached the cortex, the cortical layers were disrupted. In the patient with localized cortical dysplasia, a complete disorganization of the cortical lamination was found, and numerous neurons were also present in the white matter. Disoriented pyramidal neurons weakly labelled with cytoskeletal neuronal markers were also present but no cytomegalic cells were found. One of the patients with nodular heterotopia underwent only partial resection of both the 'epileptogenic area' and of the lesion; this patient still presents with seizures. The other patient with nodular heterotopia is seizure-free after a complete lesionectomy and excision of the epileptogenic area. The third patient, with focal cortical dysplasia, had two surgeries; she became seizure-free only after the excision of the epileptogenic area detected by SEEG recording. The present data suggest that the dysplastic areas identified by MRI should not be considered as the only place of origin of the ictal discharges. From the neuropathological point of view, the focal cortical dysplasia can be considered as a pure form of migrational disorder. However, the presence of large aggregates of neurons interspersed within the white matter, in the subcortical nodular heterotopia, suggests that a defect of neuronal migration could be associated with an exuberant production of neuroblasts and/or a disruption of mechanisms for naturally occurring cell death.     

Increased density of microtubule associated protein 2-immunoreactive neurons in the prefrontal white matter of schizophrenic subjects

Recent studies have suggested that schizophrenia may be related to prenatal disturbances in the cortical subplate, a transient but essential structure in the formation of cerebral cortical circuitry. Although most subplate neurons die during later development, some remain as the interstitial neurons of the adult white matter. In this study we used a monoclonal antibody against the cytoskeletal protein, microtubule associated protein-2 (MAP2), to quantify the density and distribution of labeled neurons in postmortem brain specimens containing the prefrontal white matter from five schizophrenic cases and matched controls. In both schizophrenics and matched controls, the density of white matter neurons decreased with increasing white matter depth. However, the mean density of MAP2-immunoreactive neurons was greater in the superficial white matter of the schizophrenic subjects compared to the matched controls. In contrast, no difference in the density of labeled neurons was seen in the deeper white matter. These findings are consistent with an abnormality in the development of the cortical subplate in at least some cases of schizophrenia.     

Vasculogenesis from embryonic bodies of murine embryonic stem cells transfected by Tgf-beta1 gene

Alzheimer's disease (AD) is a progressive disorder associated with disruption of neuronal function and neuronal loss. N-acetylaspartate (NAA) is a marker of neuronal content and can be assessed using proton (1H) magnetic resonance spectroscopy (MRS). We utilized 1H-MRS (two-dimensional chemical-shift imaging) to assess amplitudes and areas of NAA, as well as choline moieties (Cho), creatine (Cr) and myo-inositol (mI), in 15 AD patients compared with 14 control subjects. Voxels were classified as predominantly cortical gray matter (CGM), subcortical gray matter (SGM), or white matter (WM). Compared with control subjects, AD patients exhibited decreased NAA/Cho and NAA/Cr amplitudes, whereas an increase was observed in Cho/Cr and in amplitude ratios involving mI. Area ratios were significant in the same direction for NAA/Cho, NAA/Cr, mI/Cr and mI/NAA. No significant effects of tissue type were observed; however, significant group x tissue type interactions were noted for Cho/Cr and mI/Cr amplitudes. Our study confirms that 1H-MRS can identify distinct physicochemical alterations in AD patients, reflecting membrane changes and diminished neuronal function. These alterations can be used as longitudinal markers for the disease.     

Subcortical arteriosclerotic encephalopathy (Binswanger's type) and cortical infarcts in a young normotensive patient

A 49-year-old normotensive man died after a series of strokes, slowly evolving dementia and personality change occurring over a period of 23 years. CT scan showed large infarcts involving the cortex and white matter of the temporo-occipital areas, small subcortical infarcts and low attenuation in the white matter of the frontal and parietal lobes. Neuropathological examination revealed large cortical and small subcortical infarcts corresponding to the radiological findings as well as degeneration/demyelination of central white matter corresponding to the areas of low attenuation seen on CT. The basic underlying pathological process was hyaline arteriosclerosis and atheroma which diffusely affected the small intracerebral arteries and to a lesser extent the arteries of the circle of Willis. Though usual because of the absence of hypertension, the very early age at onset of the syndrome and the presence of large cortical infarcts this case illustrates the clinical, radiological and neuropathological features of subcortical arteriosclerotic encephalopathy (Binswanger's type).     

Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse

A mouse model of traumatic brain injury was developed using a device that produces controlled cortical impact (CCI), permitting independent manipulation of tissue deformation and impact velocity. The left parietotemporal cortex was subjected to CCI [1 mm tissue deformation and 4.5 m/s tip velocity (mild), or 6.0 m/s (moderate)] or sham surgery. Injured animals showed delayed recovery of pedal withdrawal and righting reflexes compared to sham-operated controls. Significant severity-related deficits in forepaw contraflexion and performance on a rotarod device were evident for up to 7 days. Using a beam walking task to measure fine motor coordination, pronounced deficits were apparent for at least 2 and 4 weeks following mild and moderate CCI, respectively. Cognitive function was evaluated using the water maze. Impairment of place learning, related to injury severity, was observed in mice trained 7-10 days following CCI. Similarly, working memory deficits were evident in a variation of this task when examined 21-23 days postinjury. Mild CCI caused necrosis of subcortical white matter with minimal damage to somatosensory cortex. Moderate CCI produced extensive cortical and subcortical white matter damage. Triple fluorescence labeling with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), antineuronal nuclear protein (NeuN), and Hoechst 33258 of parallel sections showed frequent apoptotic neurons. These findings demonstrate sustained and reproducible deficits in sensory/motor function and spatial learning in the CCI-injured mouse correlating with injury severity. Mechanisms of neuronal cell death after trauma as well as strategies for evaluating novel pharmacological treatment strategies may be identified using this model.     

Thyroid hormones in human tumoral and normal nervous tissues

We have studied T4 and T3 concentrations, DNA and protein concentrations and 5' and 5 deiodinases in samples of brain tumors obtained at surgery from 49 patients, and, in most cases, also from surrounding normal tissue. T4 concentrations in normal cortical tissue (6.19+/-0.45 ng/g) were lower than in white matter, but the difference disappeared when referred to the DNA content (2.26+/-0.27 ng/mg DNA). No other differences were found between cortical and white matter, or among cortical lobes. T4 in normal tissue was higher than previously reported, mostly from autopsy samples, whereas T3 (0.99+/-0.07 ng/g) was similar. 5'D-I activity was negligible as compared to 5'D-II (8.11+/-1.09 fmol/h/mg protein). When expressed in relation to the different DNA contents of normal vs. tumoral tissue, 5'D-II activities were the same for both. 5D activity was highly variable in the tumoral tissue, with negligible activities in meningiomas and pituitary adenomas. When referred to the DNA content, T4 and 5'D-II were the same, but T3 concentrations were lower in the tumor (0.24+/-0.03 ng/mg DNA) as compared to normal (0.35+/-0.04 ng/mg DNA) tissue samples. Whether or not this decrease of T3 affects the expression of T3-sensitive processes remains to be studied.     

Neuropathological findings in eight children with cerebro-oculo-facio-skeletal (COFS) syndrome

Cerebro-oculo-facial-skeletal (COFS) syndrome is a rare autosomal recessive disorder with microcephaly, severe mental retardation, and death in childhood. The pathogenesis is unknown. Neuropathological features of 8 children with COFS syndrome are presented. Seven of the children, ranging in age from 36 weeks gestation to 5 years 8 months, are of North American aboriginal background from Manitoba, Canada. The eight child is a 3-year-old Caucasian male. In all children there was severe microencephaly and mild ventriculomegaly. Cerebral myelination appeared to be delayed in one infantile case. Swollen ubiquitinated granular cells appeared in the white matter shortly after birth. Older children displayed cortical neuron loss, patchy or diffuse absence of myelin and gliosis in the white matter, and pericapillary and parenchymal mineralization in the globus pallidus and to a lesser extent the putamen and cerebral cortex. The cerebellum of older children exhibited severe degenerative changes involving the internal granular layer and Purkinje cell layer. The neuropathological changes, previously not well documented, suggest that COFS syndrome is associated with a degenerative process that begins in utero and affects many brain cell types. Similarities to Cockayne syndrome are discussed.     

Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin-deficient jimpy mouse

Jimpy is a shortened life-span murine mutant whose genetic disorder results in severe pathological alterations in the CNS, including hypomyelination, oligodendrocyte death and strong astroglial and microglial reaction. The knowledge of metallothionein (MT) regulation in the CNS and especially of MT presence in specific glial cell types under pathological conditions is scarce. In the present study, immunocytochemical detection of MT-I + II has been performed in spinal cord sections from 10-12- and 20-22-day-old jimpy and normal animals. The identification of MT-positive glial cells was achieved through double labeling combining MT immunocytochemistry and selective markers for oligodendrocytes, astrocytes and microglia. MT was found in glial cells and was present in the spinal cord of jimpy and normal mice at both ages, but there were remarkable differences in MT expression and in the nature of MT-positive glial cells depending on the type of mouse. The number of MT-positive cells was higher in jimpy than in normal spinal cords. This was apparent in all spinal cord areas, although it was more pronounced in white than in the gray matter and at 20-22 days than at 10-12 days. The mean number of MT-positive glia in the jimpy white matter was 1.9-fold (10-12 days) and 2.4-fold (20-22 days) higher than in the normal one. Astrocytes were the only parenchymal glial cells that were positively identified as MT-producing cells in normal animals. Interestingly, MT in the jimpy spinal cord was localized not only in astrocytes but also in microglial cells. The occurrence of MT induction in relation to reactive astrocytes and microglia, and its role in neuropathological conditions is discussed.     

Deficits in gray matter volume are present in schizophrenia but not bipolar disorder

Studies using magnetic resonance (MR) imaging have provided strong evidence that patients with schizophrenia as a group have structural brain abnormalities, including enlarged ventricles and sulci as well as smaller cortical gray matter volumes. This study was undertaken to investigate whether the brain abnormalities found in schizophrenia could be distinguished from those seen in bipolar disorder. The MR scans of 23 patients with schizophrenia were compared to those of 17 healthy community volunteers and 14 patients with bipolar disorder. Images were processed using computer-based image processing techniques to generate quantitative measures of cerebrospinal fluid (CSF), gray matter and white matter volumes. Compared to the community volunteers, the schizophrenia group had larger total CSF volumes while the bipolar group had larger ventricles. Smaller cortical gray matter volumes were found in the schizophrenia group, but not in the bipolar group. The schizophrenia group had regional deficits in gray matter volumes in comparison with both the community volunteers and the bipolar group. These findings suggest that the brain tissue abnormalities found in schizophrenia and bipolar disorder may be distinguishable using MR imaging.     

Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic spasms and focal cortical dysplasia. Report of three Italian cases in two families

We report clinical, EEG and neuroimaging findings of three patients in two Italian families with merosin-negative congenital muscular dystrophy (CMD), drug-resistant occipital epilepsy, diffuse persistent cerebral white matter changes and focal cortical dysplasia. Clinical and epilepsy histories, EEG and neuroimaging findings were very similar in all patients. Seizures started in childhood and mainly consisted of periodic spasms, a particular type of partial seizure characterized by clusters of epileptic spasms. The motor expression of the spasms was very mild so that they had been frequently missed or misinterpreted as non-convulsive generalized absence seizures. Interictal EEG showed occipital spike-waves and bilateral synchronous slow spike-wave discharges. Ictal EEG showed prolonged periodic sequences of slow waves with associated fast rhythm complexes, characteristic of periodic spasms. Two patients had normal intelligence, one patient presented moderate mental retardation. Focal cortical dysplasia in the posterior areas of the brain, in addition to marked diffuse white matter alterations, was detected in the magnetic resonance images of all patients. Findings in these patients indicate that in merosin-negative CMD brain involvement can include cortical dysplasia, in addition to white matter changes. In such cases the brain damage can lead to a childhood-onset localization-related symptomatic occipital epilepsy. Epileptic seizures and cortical dysplasia can be, however, difficult to detect in CMD. The clinical semiology of epileptic seizures may in fact be modified because of muscular weakness. This implies that epilepsy may be misdiagnosed or even missed and EEG-polymyographic recordings may be necessary to identify it. Similarly, cortical dysplasia may be very localized and visible by neuroimaging only if it is carefully investigated on the basis of epileptological and EEG-polymyographic findings.     

Declarative and procedural learning, quantitative measures of the hippocampus, and subcortical white alterations in Alzheimer's disease and ischaemic vascular dementia

This research investigated whether subjects with Alzheimer's disease (AD) and ischaemic vascular dementia (IVD) associated with periventricular and deep white matter alterations can be dissociated on tests of declarative and procedural memory, as well as on MRI indices of white matter alterations and the size of the hippocampal formation. The California Verbal Learning Test (CVLT) and the Pursuit Rotor Learning Tests (PRLT) were used to measure declarative and procedural memory, respectively. Subjects with IVD obtained a higher score on the CVLT recognition discriminability index; however, on the PRLT total time on target, carry-over between trial blocks, and slope calculated for all test trials was low. Subjects with AD exhibited the opposite profile. MRI studies indicated that subjects with IVD had considerably greater white matter alterations, but larger hippocampal formations than subjects with AD. Higher scores on the CVLT recognition discriminability index were correlated with increased size of the body of the hippocampus and parahippocampal gyrus. By contrast, as the severity of white matter alterations increased the slope on the PRLT declined. In sum, subjects with AD and IVD can be dissociated on the basis of differing patterns of impairment on tests of declarative and procedural memory, and MRI indices of white matter alteration and the integrity of the hippocampal formation.     

Feasibility of ultrasound hyperthermia in the treatment of malignant brain tumors

In order to test the biological feasibility of using ultrasound-generated hyperthermia for the treatment of brain tumors, damage threshold studied and thermal dosimetry studies as a function of temperature were performed in 44 acute experiments in cats. Bilateral craniotomies were performed to expose the dural surface. Ultrasonic radiation was applied for 50 minutes at different intensities to generate temperatures up to 48 degrees C. Thermal fields were mapped using an electrode array of three triple-junction thermocouple probes. Each probe left a track easily identified histologically. Serial sections of each brain were cut and stained, allowing for precise correlation of histology and thermocouple location and temperature. At temperatures of less than 42 degrees C for 50 minutes, no evidence of damage could be detected in either gray or white matter. At 43 degrees C partial loss of neurons was seen in the brain adjacent to the probe, but at the same temperature in white matter, only edema was seen. At temperatures of 44-45 degrees C there was definite loss of both neurons in the gray matter and myelin tracts in the white matter. The lesions created by using ultrasound-generated hyperthermia were sharply marginated. This sharp demarcation histologically correlated well with the abrupt fall off in temperature as a function of distance from the lesion edge. The results of this study are important in two respects. First, it demonstrates that ultrasound can effectively heat the brain in an extremely controlled and precise manner. Second, the brain can withstand temperatures to 42 degrees C without showing histological evidence of damage, which is the temperature range at which neoplastic cells begin to show cytotoxic effects.     

Cortical visual impairment following bacterial meningitis: magnetic resonance imaging and visual evoked potentials findings in two cases

Cortical visual impairment (CVI) following bacterial meningitis is a very uncommon complication. Two children with CVI following bacterial meningitis are reported. Bacterial agents were Haemophilus influenzae type B in one and meningococci in the other child. Both children showed only insufficient recovery from CVI, mental retardation and residual neurological symptoms. Flash visual evoked potentials (VEP) showed preserved cortical response at onset of CVI. Re-evaluations several months later showed significantly reduced amplitudes, but normal latencies for P100. Thus, flash VEP does not allow prediction of visual outcome. MRI results have not been reported before. MRI at onset of diagnosis showed occipital parenchymal irregularities with enlarged sulci and subarachnoid spaces. Follow up MRI 15 months after onset of CVI in one patient showed marked atrophy of the occipital cortex, hyperintensities of the cortical white matter and no visible optic radiation. The MRI findings indicate hypoxic-ischaemic lesions in the border zone between the distribution of the great cerebral arteries.     

Abundance of the longer A beta 42 in neocortical and cerebrovascular amyloid beta deposits in Swedish familial Alzheimer's disease and Down's syndrome

Recent studies have demonstrated the deposition of amyloid beta (A beta) protein with carboxyl- and aminoterminal heterogeneity in cortical and cerebrovascular deposits of Alzheimer's disease (AD). Using carboxyl end-terminal specific antibodies to A beta peptides, we examined the immunocytochemical distribution of A beta 40 and A beta 42 species in brain tissue from a Swedish subject with familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid beta precursor protein (A beta PP), and from subjects with Down's syndrome and sporadic AD. In the Swedish subject, we found profound parenchymal A beta deposits and cerebral amyloid angiopathy in all four cortical lobes and cerebellum. A beta 42 was evident in almost all parenchymal deposits as well as many vascular deposits. Although A beta 40 was present in meningeal and intraparenchymal vessels, deposits containing this shorter peptide reactivity were sparse. Surprisingly, our observations in Swedish FAD showing a remarkable abundance of A beta 42 in both parenchymal and vascular deposits were qualitatively similar to the Down's syndrome and most sporadic AD cases, and to previously published A beta PP717 FAD. While previous transfection studies in different cell cultures indicate substantially increased soluble A beta production and A beta 40 species to be predominant, it would appear that the double A beta PP mutations in Swedish FAD largely result in the deposition of the longer A beta 42 in vivo.     

Pathways of migration of transplanted Schwann cells in the demyelinated mouse spinal cord

We have studied the behavior of Schwann cells transplanted at a distance from an induced myelin lesion of the adult mouse spinal cord. These transplanted cells were mouse Schwann cells arising from an immortalized cell line (MSC80) which expresses several Schwann cell phenotypes including the ability to produce myelin. The behavior of MSC80 cells was compared to that of purified rat Schwann cells transplanted in the same conditions. Schwann cells were labeled in vitro with the nuclear fluorochrome Hoechst 33342 and were transplanted at distances of 2-8 mm from a lysolecithin-induced myelin lesion in the spinal cord of shiverer and normal mice. Our results show that transplanted MSC80 cells migrated toward the lesion, in both shiverer and normal mouse spinal cord, preferentially along the ependyma, meninges, and blood vessels. They also migrated along white matter tracts but traveled a longer distance in shiverer (8 mm) than in normal (2-3 mm) white matter. Using these different pathways, MSC80 cells arrived within the lesion of shiverer and normal mouse spinal cord at the average speed of 166 microns/hr (8 mm/48 hr). Migration was most efficient along the ependyma and the meninges where it attained up to 250 microns/hr. Migration was much slower in white matter tracts (95 microns/hr +/- 54 in the shiverer and only 38 microns/hr +/- 3 in the normal mouse). We also provide evidence for the specific attraction of MSC80 cells by the lysolecithin-induced lesion since 1) their number increased progressively with time in the lesion, and 2) MSC80 cells left their preferential pathways of migration specifically at the level of the lesion. Finally, combining the Hoechst Schwann cell labeling method with the immunohistochemical detection of the peripheral myelin protein, P0, we show that some of the MSC80 cells which have reached the lesion participate in myelin repair in both shiverer and normal lesioned mouse spinal cord. A series of control experiments performed with rat Schwann cells indicate that the migrating behavior of transplanted MSC80 cells was identical to that of purified but non-immortalized rat Schwann cells.     

Backbone mutations in transmembrane domains of a ligand-gated ion channel: implications for the mechanism of gating

The relationship between regional parenchymal cerebral blood volume (CBV), regional cerebral blood flow (CBF) and the calculated mean transit time (MTT) was investigated in 14 newborn piglets. The effects of combined hypoxic hypoxia (PaO2 = 32 +/- 5 mm Hg) and hypercapnia (paCO2 = 68 +/- 5 mm Hg) were measured in seven animals. Remaining animals served as the control group. During baseline conditions the highest CBF and CVB values were found in the lower brainstem and cerebellum, whereas white matter exhibited the lowest values (p < 0.05). MTT was prolonged within the cerebral cortex (2.34 +/- 0.42 s-1) compared with the thalamic MTT (1.53 +/- 0.38 s-1) (p < 0.05). Under moderate hypoxia/hypercapnia, a CBF increase to the forebrain (p < 0.05) resulted in an elevated brain oxygen delivery (p < 0.05) and so CMRO2 remained unchanged. Moreover, a moderate increase of CBV and a marked shortening of MTT occurred (p < 0.05). The CBV increase was higher in structures with lowest baseline values, i.e., thalamus (66% increase) and white matter (62% increase) (p < 0.05). MTT was between 22% of baseline in the lower brainstem and 49% in white matter (p < 0.05). We conclude that under normoxic and normocapnic conditions the newborn piglets exhibit a comparatively enlarged intraparenchymal CBV. Moderate hypoxia and hypercapnia induced a marked increase in cerebral blood flow which appears to be caused by an increased perfusion velocity, expressed by a strongly reduced mean transit time and by a concomitant CBV increase.     

Scaling of cortical neuron density and white matter volume in mammals

A prior scaling model, based on repeating cortical units, whose number and size increase with brain size, gave discrete exponents for cortical thickness (1/9), outer (visible) surface area (2/3), folded cortical surface area (8/9) and cortical volume (1), each as a function of brain volume. These exponents are in reasonable agreement with a diversity of empirical data (Prothero, 1997). Rockel et al. (1980) reported that neuron number, assayed in a narrow column across cortex (pia to white matter) is invariant over several differing brain regions and species. Since cortical thickness scales, empirically, as about the 1/9 power of brain volume, their data imply that neuron line density (across cortex) scales with an exponent of about -1/9. Rockel et al. (1980) also urged that cortical neuron surface density is invariant. This extrapolation implies that neuron volume density scales, like line density, as the -1/9 power of brain volume, in marked disparity with the data of Haug (1987) and Tower (1954). The present model assumes an invariant number of neurons per repeating unit. Thus neuron number, assayed across cortical thickness, is independent of brain size, in accord with Rockel et al. (1980). The model predicts that neuron line density (in any direction) scales as the -1/9 power of brain volume. Now neuron volume density scales as the -1/3 power of brain volume, in reasonable agreement with the results of Haug (1987) and Tower (1954). For white matter, I assume that mean axon length scales with brain diameter (exponent of 1/3). The number of white matter axons scales in proportion to the number of repeating units (exponent of 2/3). Given an invariant size distribution of white matter axons, white matter volume thus scales with an exponent of one, in reasonable accord with Haug (1970).     

Increased immunoreactivities for the basic fibroblast growth factor and its receptor in astrocytes at the site of cerebral lesions and oedematous change in SHR

1. To obtain information about changes of basic fibroblast growth factor (bFGF) in the brain in chronic hypertension, we immunohistochemically studied the distribution and level of bFGF and its receptor in the brain of stroke-prone spontaneously hypertensive rats (SHRSP). 2. In the control normotensive rats, immunoreactivity for bFGF was demonstrated in nerve cells, while there was almost no reactivity in astrocytes. 3. In SHRSP, there was a marked immunoreactivity in the densely accumulated reactive cells, particularly astrocytes, in and around cerebral cortical lesions. Slightly increased reaction for bFGF was found in the nerve cells around lesions. Astrocytes in the subcortical white matter on both ipsi- and contralateral sides of the cortical lesion also showed immunoreactivity for bFGF. The location of increased bFGF expression in SHRSP corresponded very well with the site of extravasated plasma fluid demonstrated by anti-fibrinogen antibody. Electron microscopically, bFGF was shown in astrocytes along the rough endoplasmic reticulum suggesting the growth factor to be produced in the cells and not to be taken up from the surroundings. Expression of FGF-receptor was also demonstrated in reactive astrocytes in the oedematous cortical portion around lesion and in the oedematous subcortical white matter. 4. These findings indicate the possibility that oedema and the simultaneously generated free radicals or some extravasated plasma components express bFGF in astrocytes and probably in nerve cells as well as FGF-receptor in astrocytes, and that the thus expressed bFGF and its receptor play some role in the sequence of developmental events of hypertensive cerebral lesions.     

Changes in cerebral blood flow and oxygen metabolism related to magnetic resonance imaging white matter hyperintensities in Alzheimer's disease

We studied changes in cerebral perfusion and oxygen metabolism to elucidate the pathophysiological nature and clinical significance of white matter hyperintensities in Alzheimer's disease (AD). METHODS: Sixteen AD patients (age 71.6 +/- 3.1 yr) whose T2-weighted MR images showed white matter hyperintensities, and 16 age-matched AD patients (age 71.0 +/- 4.3 yr) without white matter hyperintensities were compared. Regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) were measured by using (15)O steady-state method and PET. RESULTS: There was no significant difference in cognitive impairment between the two groups. Compared to the patients without white matter hyperintensities, those with them had significantly low CBF values and significantly high OEF values in all cortical and white matter regions. However, there were no significant differences in CMRO2 values between the two groups. Severity of white matter hyperintensities correlated with the mean cortical and mean white matter OEF. CONCLUSION: In AD patients, white matter hyperintensities on T2-weighted MR images represent ischemic changes in which oxygen metabolism and function are fairly compensated. These changes are not disease-specific but are age-associated coincidences, as in normal aging with or without vascular risk factors.     

Creating connected representations of cortical gray matter for functional MRI visualization

We describe a system that is being used to segment gray matter from magnetic resonance imaging (MRI) and to create connected cortical representations for functional MRI visualization (fMRI). The method exploits knowledge of the anatomy of the cortex and incorporates structural constraints into the segmentation. First, the white matter and cerebral spinal fluid (CSF) regions in the MR volume are segmented using a novel techniques of posterior anisotropic diffusion. Then, the user selects the cortical white matter component of interest, and its structure is verified by checking for cavities and handles. After this, a connected representation of the gray matter is created by a constrained growing-out from the white matter boundary. Because the connectivity is computed, the segmentation can be used as input to several methods of visualizing the spatial pattern of cortical activity within gray matter. In our case, the connected representation of gray matter is used to create a flattened representation of the cortex. Then, fMRI measurements are overlaid on the flattened representation, yielding a representation of the volumetric data within a single image. The software is freely available to the research community.