The major defining pathological hallmarks of Alzheimer's disease (AD) are the accumulations of Abeta in senile plaques and hyperphosphorylated tau in neurofibrillary tangles and neuropil threads. Recent studies indicate that rather than these insoluble lesions, the soluble Abeta oligomers and hyperphosphorylated tau are the toxic agents of AD pathology. Such pathological protein species are accompanied by cytoskeletal changes, mitochondrial dysfunction, Ca2+ dysregulation, and oxidative stress. In this review, we discuss how the binding of Abeta to various integrins, defects in downstream focal adhesion signaling, and activation of cofilin can impact mitochondrial dysfunction, cytoskeletal changes, and tau pathology induced by Abeta oligomers. Such pathological consequences can also feedback to further activate cofilin to promote cofilin pathology. We also suggest that the mechanism of Abeta generation by the endocytosis of APP is mechanistically linked with perturbations in integrin-based focal adhesion signaling, as APP, LRP, and beta-integrins are physically associated with each other.
Alzheimer Disease ; Amyloid ; Cytoskeleton ; Endocytosis ; Focal Adhesions ; Integrins ; Mitochondria ; Neurofibrillary Tangles ; Neuropil Threads ; Oxidative Stress ; Plaque, Amyloid

Here we present an autopsy case of chronic traumatic encephalopathy (CTE) in a 36-year-old man. He had a history of febrile seizures at the age of four and was severely demented at age 10 when he was admitted to a mental hospital. He had suffered repetitive self-harm, such as frequent banging of the head on the wall in his hospital record, but he had no clear history between the ages of four and ten. Autopsy revealed global cerebral atrophy, including the basal ganglia, thalamus, hippocampus, amygdala, mammilary bodies and lateral geniculate bodies. This case showed typical pathological features of CTE. Phosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs) and neuropil threads (NT) we are widely distributed in the brain, especially in the depth of the cerebral sulci. NFT and NT were also found in the basal ganglia, thalamus, amygdala and brainstem. Scanty β-amyloid deposits were found in the motor and sensory cortices, but α-synuclein was completely negative in the brain. This example showed that CTE can occur in young ages and that even children can experience CTE dementia.
Adult ; Amygdala ; Atrophy ; Autopsy* ; Basal Ganglia ; Brain ; Brain Injuries ; Brain Injury, Chronic* ; Brain Stem ; Child* ; Dementia ; Geniculate Bodies ; Head ; Hippocampus ; Hospital Records ; Hospitals, Psychiatric ; Humans ; Neurofibrillary Tangles ; Neuropil Threads ; Pathology ; Seizures, Febrile ; Thalamus

The present study involves a chronological and comparative analysis of both microtubule-associated protein 1A (MAP1A) and microtubule-associated protein 2 (MAP2) immunoreactivities in the striatum of both seizure resistant (SR) and seizure sensitive (SS) gerbil. The MAP1A immunoreactivity is weakly detected in perikarya of SR gerbils. However, MAP1A immunoreactivity is more accumulated in perikarya and dendrites in the pre-seizure group. At 30 min postictal, MAP1A immunoreactivity in the perikarya is decreased. At 3 hr postictal, MAP1A immunoreactivity in perikarya and dendrites is similarly decreased to the level of SR gerbils. The MAP2 immunoreactivity is weakly detected in the perikarya and dendrites of SR gerbils. However, MAP2 immunoreactivity is more accumulated in perikarya and dendrites. In particular, the neuropil between unstained fiber tracts obviously contains strong MAP2 immunoreactivity. At 30 min postictal, MAP2 immunoreactivity isn't almost observed in striatum. At 3 hr postictal, the MAP2 immunoreactivity is not different in the 30 min post -seizure groups but is only observed in the neuropil. However, at 12 hr postictal, the decrease of both MAP1A and MAP2 immunoreactivities had recovered to the pre -seizure level of SS gerbils. These results suggest that MAPs immunoreactivity in the striatum is different in SR and SS gerbils, and that this difference may be the results of seizure activity in this animal.
Animals ; Dendrites ; Epilepsy ; Gerbillinae* ; Microtubule-Associated Proteins* ; Microtubules* ; Neuropil ; Seizures*

PURPOSE: To correlate the serial findings obtained by diffusion- and T2-weighted imaging with histologicfind-ings obtained from 30 minutes to 31 days after the development of cerebral infarction in rabbits. MATERIALS AND METHODS: Nineteen male New Zealand white rabbits were subjected to intracerebral embolic infarction.Diffusion- and T2-weighted imagings were performed at 30 min, 2, 4 and 6 hours, and 1, 3, 5, 7, 11, 21 and 31days. Apparent diffusion coefficient (ADC) ratios and T2 signal intensity ratios of infarcted and normal brainwere calculated. Microphotographic or electron microscopic (EM) examinations were performed during hyperacute,acute and chronic infarctions. RESULTS: During hyperacute infarction, diffusion-weighted images showed highsignal intensity in the infarcted area, and ADC ratios ranged from 0.81 to 0.56. High signal intensity ondiffusion-weighted images continued until day 3, decreasing thereafter. The ADC ratio increased continuouslyafter day 1. High signal intensity on T2-weighted images was noted from 6 hours and continued until day 7,decreasing thereafter. Microphotographic findings at 6 hours were normal, but EM examination revealed cellularswelling with intact basement membrane, suggesting cytotoxic edema. During acute infarction, abnormal dilatationof the perineural space, cell destruction, and loosening of the neuropil matrix were revealed bymicrophotography. During chronic infarction, microphotographic and EM findings revealed liquefaction necrosis. CONCLUSION: These data indicate that in cases of hyperacute infarction, diffusion-weighted images reflectcy-totoxic edema more accurately than do T2-weighted images. A gradually increasing ADC ratio during the course ofinfarction may be associated with vasogenic edema and cell lysis.
Basement Membrane ; Cerebral Infarction* ; Diffusion ; Edema ; Humans ; Infarction ; Male ; Necrosis ; Neuropil ; Rabbits

To understand the changes in expression of calcium binding proteins(CaBP) during the experimental focal ischemia, expression of two kinds of CaBP, paralvumin(PV) and calbindin D-28K(Calbindin), immunocytochemically, and activities of cytochrome oxidase(CO) and acetylcholinesterase(AchE), histochemically, in focal ischemic brain of the rat were investigated. Two groups of focal ischemic infarction were produced in Sprague Dawley rats(200-350 mg):Group I, Clip compression of left middle cerebral artery(MCA) for 5-10 mins and release;Group II, Electric coagulation of left MCA for 2-24 hrs. In the group I, CO activity and PV- and Calbindin-immunoreactivity(IR) were decreased in the left MCA territory, and decreased in number of PV- and Calbindin-IR neurons and degree of IR, but AchE activity was nearly same as that of control cortex. In the group II, decrease of CO and AchE activities, and marked increase of PV- and Calbindin IRs were noted on neuropil in the layers I through VI of ischemic region. Characteristically pyramidal cells, which did not express the both CaBPs in the control cortex, of layer V of ischemic cortex showed PV- and Calbindin Irs in the cell body and apical dendrite. These findings suggest that 1) PV- and Calbindin-IR neurons, mainly non-pyramidal cells, are more vulnerable than pyramidal cell to ischemic injury, 2) CaBP may have some roles in hypoxic neuronal injury, and 3) PV and Calbindin-immunocytochemistry can be used as useful technique in evaluation of experimental ischemia.
Animals ; Brain ; Calbindins ; Calcium ; Cytochromes ; Dendrites ; Infarction ; Ischemia* ; Neocortex* ; Neurons* ; Neuropil ; Pyramidal Cells ; Rats*

We report a case of extraventricular neurocytoma(left parietal lobe) in a young man presented with hemiparesis. The tumor, a radiologically well-circumscribed, cystic and enhancing mass, was partially removed. The patient, who received postoperative radiotherapy, is living well after 15 months of follow-up. Pathology showed a well-differentiated lesion composed of uniform, round cells with perinuclear halos in a neuropil background, immunohistochemically positive for neuronal markers. This was a cystic extraventricular neurocytoma(glio-neuronal tumor) arising from the left parietal lobe. Its features were consistent with neurocytoma pathologically and were different from those of intraventricular neurocytoma pathophysiologically. We outline the morphological and immunohistochemical evaluations necessary to recognize this rare tumor.
Follow-Up Studies ; Humans ; Neurocytoma* ; Neurons ; Neuropil ; Paresis ; Parietal Lobe ; Pathology ; Rabeprazole ; Radiotherapy ; Synaptophysin

The presence and distribution of pan-neuroendocrine markers such as neuron-specific enolase (NSE), chromogranin (CG), and synaptophysin (SYP) were investigated by immunohistochemistry in 15 cases of neuroblastic tumors, including four cases of neuroblastomas, six cases of ganglioneuroblastomas, and five cases of ganglioneuromas. Three cases of normal sympathetic ganglion were used for the normal control group. NSE was observed in all cases and both in ganglion cells and in neuropils. NSE was detected not only in the majority of the neuroblasts showing signs of differentiation, but also in some poorly differentiated neuroblasts. All cases of neuroblastic tumors were positive for CG, however, some variability of staining intensity and distribution patterns were noted. CG was found mainly in differentiated neuroblasts with enlarged cytoplasm and nuclei along the periphery of the perikaria, and was also found in the perinuclear regions of some undifferentiated cells. SYP was positive in 9 of 11 cases. In all of the 9 cases, SYP was detected in some differentiating neuroblasts and differentiated neuroblasts, as well as the mature ganglion cells. However, it has scarcely stained in dot or granular pattern. Two CG-negative tumors were also negative for SYP. Our data indicate that antibodies against NSE and CG are helpful as a diagnostic aid for neuroblastic tumors.
Antibodies ; Cytoplasm ; Ganglia, Sympathetic ; Ganglion Cysts ; Ganglioneuroblastoma ; Ganglioneuroma ; Immunohistochemistry ; Neuroblastoma ; Neurons* ; Neuropil ; Phosphopyruvate Hydratase* ; Synaptophysin*

This study examined and compared the immunocytochemical distribution of the two calcium-binding proteins calbindin D-28k and parvalbumin in the sensory and motor cortex of the cat. In this experimental animal, calcium-binding protein calbindin D-28k immunoreactive neurons were mainly found many pyramidal cells distributed in layers 2 and 3 of the two cortical areas. Calbindin D-28k neuropil labeling was heaviest in layers 1 to 3. In contrast to parvalbumin, we found only minor differences in distribution, size and mor-phology of calbindin D-28k cell body or neuropil staining in the two cortical areas. Parvalbumin- immunoreactive cells were in all layers cortex except layer 1 and reached their peak density in the middle layers. The two cortical areas differed markedly in number, cell size and morphology of immunoreactive cells. Parvalbumin positive cells were more than twice as numerous in the two cortical areas compared to the calbindin D-28k positive cells. Calbindin D-28k and parvalbumin-immunoreactive somata were round, oval, spindle and polygonal in shape, and the positive neurons were unipolar, bipolar,multipolar and horizontal in shape. The diameters of the somata of the two positive neurons were 15~20 micrometer. Also, two positive dendrites were considerably densely arrayed in arborization.
Animals ; Calbindins* ; Calcium-Binding Proteins ; Cats* ; Cell Count ; Dendrites ; Motor Cortex* ; Neurons ; Neuropil ; Pyramidal Cells

Neuroglial cells are actively participate in the pathogenesis or in the recovery procedures following brain lesions. The study was performed to evaluate the plasticity of glial cells following different degree of brain lesions. Neurosurgical operations were made on the rats fixed on the stereotaxic apparatus. Tissue column of 3 mm-diameter was isolated in the caudatoputamen with concomitant severe bleeding in the first group. In the second group, the sensorimotor cortex was suctioned out with moderate bleeding. In the third group, the mammillary body was electrically coagulated with minimal bleeding. Caudatoputamens, as a lesioned tissue or as a target tissue of lesioned area, were studied light and electron microscopically. Observations on reactivities and plasticities of neuroglial cells on the different situations, the following results were obtained : 1. Astrocytes were swollen within an hour following brain lesions. 2. In case of smaller lesion, astroglia alone remove altered structures. 3. Microglia are increased in number, if the lesion is large with severe bleeding. The microglia might come from blood monocyte via transformation to pericyte. 4. In large lesion, astroglia were greatly hypertropied, and microglia might be moving and functioning effeciently within the hypertropied cytoplasm of astroglia. 5. In the stabilizing stage, astroglia produce glial fibers and fix the exhausted microglia. Fixed microglia are proceed into apoptotic process in the cytoplasm of astroglia and removed by them. All these procedures might be controlled by various receptors and secretions of astroglia. It means that astroglia is not only the basic supporting element of nervous tissue, but also an actively functioning element for the most effective homeostatic functioning of the neuropil.
Animals ; Apoptosis ; Astrocytes ; Brain* ; Cytoplasm ; Hemorrhage ; Mamillary Bodies ; Microglia ; Monocytes ; Neuroglia* ; Neuropil ; Pericytes ; Plastics* ; Rats ; Suction

This study was examined and compared the immunocytochemical distribution of the two calcium-binding proteins calbindin D-28K and parvalbumin immunreactive neurons in the medulla oblongata and spinal cord after transection of spinal cord in rats. In this experiment, calbindin D-28K immnunoreactive neurons were mainly found in many pyramidal cells distributed medulla oblongata and spina1 cord of rats. Parvalbumin immunoreactive cells were demonstrated in all lamina of the gray matter of the spinal cord. These immunoreactive cells had the most high density in the severa1 nuclei of the ventra1 horn of the all segments of the spina1 cord. Calbindin D-28K neuropil labeling was strongly noted in spina1 all segments of the spinal cord. In contrast parva1bumin immunoreactive, little differences were found in distribution, size and morphology of calbindin D-28K cell body or neuropil staining in the spinal cord. The number of parvalbumin immunoreactive cells were more than twice in the medulla oblongata and spinal cord compared to the calbindin D-28K immunoreactive cells. Calbindin D-28K and parvalbumin-immmoreactive somata were round, ova1, spind1e and polygona1 in shape, and the immunoreactive neurons were unipolar, bipolar, multipolar and horizontal in shape. The diameters of the somata of the two immunoreactive neurons were 40 ~50 micrometer, respectively. Also dendrites of two immunoreactive neurons were densely arrayed in network. These results suggest that CB-IR and PV-IR most high density in the of the VII~X layers in the ventra1 horn of the all segments of the spina1 cord.
Animals ; Calbindins* ; Calcium-Binding Proteins ; Dendrites ; Horns* ; Medulla Oblongata* ; Neurons* ; Neuropil ; Pyramidal Cells ; Rats* ; Spinal Cord Injuries* ; Spinal Cord*