Alzheimer's disease (AD), the cause of one of the most common types of dementia, is pathologically characterized by cholinergic deficits, extracellular amyloid deposit, intraneuronal neurofibrillary tangles, gliosis, and neuronal and synaptic loss. The primary clinical manifestation of AD is a profound global dementia that is marked by severe amnesia with additional deficits in language, executive functions, attention, and visuospatial and constructional abilities. Molecular genetic studies have identified at least three genes that, when mutated, cause the autosomal dominant, early-onset familial form of the disease The late-onset, most common forms of the disease are likely to be associated with various genetic susceptibility factors. Research on the underlying pathophysiological dysfunction finally disclosed more disease-specific processes. Of particular importance is the identification and characterization of the secretases involved in endoproteolytic processing of β-amyloid precursor protein, the precursor of the amyloid β-peptide(Aβ). It is generally accepted that Aβ plays a pivotal role in the pathogenesis of AD, and that reducing brain Aβ levels may be a disease-modifying strategy. By inhibiting one or both amyloidogenic secretases and immunization with Aβ, neuropathological features of AD can be prevented or alleviated.
Alzheimer Disease* ; Amnesia ; Amyloid ; Amyloid Precursor Protein Secretases ; Brain ; Dementia ; Executive Function ; Genetic Predisposition to Disease ; Gliosis ; Immunization ; Molecular Biology* ; Neurofibrillary Tangles ; Neurons ; Plaque, Amyloid ; Presenilins

BACKGROUND: The central nervous system (CNS) is a well-known target site of steroid hormone action. Both the pyramidal neurons of Ammon's horn and the granule cells (GC) of the dentate gyrus, which have a high concentration of glucocorticoid receptors are the major targets for this hormone. Because the hippocampal formation is critically involved in memory and learning, the effects of glucocorticoid on the hippocampus are of particular interest. Chronic administration of high doses of corticosterone has been shown to directly damage to hippocampus, whereas removal of circulating glucocorticoid by adrenalectomy (ADX) may cause selective degeneration of dentate granule cells. Thus corticosterone appears to have two markedly different effects on cells of the hippocampus in rats. METHODS: In the present study, we investigate the changes in the hippocampal structures after bilateral adrenalectomy at various time points. RESULTS: Silver staining procedure selective for damaged neuronal membranes revealed degenerating neurons in dentate gyrus. Argyrophilia was specifically confine to dentate granule cells and was accompanied by the occurrence of pyknotic nuclei as observed in cresyl violet and H & E stained sections. However, on the contrary to the previous reports the neuronal loss in GC layers in dentate gyrus is variable. There were significant differences between individual rats in quantity of argyrophilia. In situ terminal transferase-mediated dUTP-nick end labeling technique (TUNEL) demonstrated that some of the ADX-induced neuronal degeneration was due to a apoptosis-related mechanism. In some of the ADX animals, NADPH-diaphorase positive neurons in the hippocampus found to be selectively lost. The latter finding should be confirmed in the subsequent experiments. CONCLUSION: These results suggest that following ADX, some of the GC undergoes neurodegeneration via apoptotic mechanism. And the present data strengthen the evidence pointing to the critical role of corticosteroids in maintaining the structural inte.
Adrenal Cortex Hormones ; Adrenalectomy* ; Animals ; Apoptosis ; Central Nervous System ; Corticosterone ; Dentate Gyrus ; Hippocampus ; Learning ; Membranes ; Memory ; Neurons* ; Rats* ; Receptors, Glucocorticoid ; Silver Staining ; Viola

Acute carbon monoxide (CO) poisoning primarily affects the central nervous system(CNS), and survivors of severe CO poisoning often suffer permanent neuropsychiatric sequelae. The most widely recognized long-term sequelae of acute CO poisoning are neurobehavioral abnormalities varying from mild personality changes, difficulty in learning and behavioral problems, to irreversible dementia. The mechanisms of these processes are poorly understood although same investigators have suggested the involvement of CO-mediated brain cerebral mitochondrial energy metabolism. Since cellular injury by almost any mechanism has the potential to accelerate free radical reactions, it appears that reactive oxygen species (ROS) may have a critical role in CO-induced brain injury. There is evidence in rats that CO vulnerable brain regions show increased production of hydrogen peroxide and hydroxyl radical after acute poisoning. On the other hand, recent evidence suggests that the novel free radical neuromodulator, nitric oxide (NO), mediates NMDA receptor-linked excitotoxicity, and that neurons that contain NO synthase (NOS) are themselves spared from NMDA and NO toxic effects. NADPH-diaphorase neurons preferentially survive in the striatum in patients with Huntington's disease, Alzheimer's disease, and relatively spared in experimental models of brain damage due to ischemia or NMDA-mediated neurotoxins. In contrast to these findings, current experiment revealed that some of NOS neuons underwent degenerative changes several days after CO exposure. Moreover, oxidative stress itself could be a mediator of apoptosis much as programmed cell death associated with experimental focal cerebral ischemia in rats. Likewise apoptosis after CO poisoning might be a cause of cell death in addition to conventional necrotic cell death. Subsequent studies are needed to verify this conjecture, which eventually can elucidate the 'biphasic' clinical features of CO poisoning.
Alzheimer Disease ; Animals ; Apoptosis ; Brain Injuries ; Brain Ischemia ; Brain* ; Carbon Monoxide Poisoning* ; Carbon Monoxide* ; Carbon* ; Cell Death ; Dementia ; Energy Metabolism ; Hand ; Humans ; Huntington Disease ; Hydrogen Peroxide ; Hydroxyl Radical ; Ischemia ; Learning ; Models, Theoretical ; N-Methylaspartate ; Neurons* ; Neurotoxins ; Neurotransmitter Agents ; Nitric Oxide Synthase* ; Nitric Oxide* ; Oxidative Stress ; Poisoning ; Rats* ; Reactive Oxygen Species ; Research Personnel ; Survivors

Bilateral acoustic neurofibrornatosis or neurofibrornatosis-2 is characterized by bilateral acoustic neurornas and it is thought to be genetically distinct from the neurohbrornatosis-1. Also called von Recklinghausen's neurofibrornatosis. We report 2 patients with neurofibrornatosis-2. Who showed progressive bilateral hearing loss, unsteady gait and headache.Neuroirnaging studies revealed bilateral cerebellopontine angle rnasses and biopsies confirmed the diagnosis.
Acoustics ; Biopsy ; Cerebellopontine Angle ; Diagnosis ; Gait Disorders, Neurologic ; Hearing Loss, Bilateral ; Humans ; Neurofibromatoses*

Alzheimer's disease (AD) is the leading cause of dementia, and the most prevalent neurodegenerative disease in the elderly. The prevalence of AD is predicted to rise as life expectancy grows across populations. The exact cause of this devastating disease is still unknown; however, it is an aging-related multi-factorial disorder, and growing evidence supports the contribution of modifiable environmental factors to unmodifiable factors such as gene and ageing itself. The recent advancement of methodologies and techniques for early diagnosis of AD facilitates the investigation of strategies to reduce the risk for AD progression in the earliest stages of the disease. Pharmacological attempts at curing, halting or modifying it have, by and large, been unsuccessful, and no breakthrough is seen in the near future. However, a lot of elements that seem to contribute to the disease such as risk factors have been identified, mainly from epidemiological and basic research studies. Many of these are amenable to lifestyle modification. Therefore, prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated dreadful neurodegenerative condition, and its associated burden for individuals and society. We provide an overview of modifiable risk factors for AD along with the supporting evidence.
Alzheimer Disease/epidemiology/*prevention & control ; Cognitive Therapy ; Dietary Supplements ; Health Behavior ; Humans ; Mind-Body Therapies ; Motor Activity ; Risk Factors

No abstract available.
*Aging ; Alzheimer Disease/drug therapy/economics/*pathology ; Cost of Illness ; Excitatory Amino Acid Agonists/therapeutic use ; Health Behavior ; Humans ; N-Methylaspartate/therapeutic use ; Risk Factors

No abstract available.
Ocular Motility Disorders* ; Tuberculosis, Meningeal*

BACKGROUND: Trimethyltin (TMT) is a neurotoxicant which produces a distinct pattern of neuronal cell death in the hippocampus following systemic administration of a single dose. However, the mechanism of selective neuronal death remains unclear. We performed this study to elucidate the underlying mechanism of TMT-induced hippocampal neu-ronal death. METHODS: The effects of trimethyltin (8.0mg/kg, I.p., single dose) on the hippocampal neurons were investi-gated in terms of changes in the neurobehavioral status, histologic, and electron microscopc findings. RESULTS: Behaviorally, TMT treatment caused stereotypic limbic system dysfunction, i.e. tremors, spontaneous seizures, vocaliza-tion, hyperactivity, hyperexcitability, intraspecific aggression as described previously. Morphologically, TMT produced prominent neurodegeneration in the dentate gyrus. Widespread, strong glial fibrillary acidic protein (GFAP) immunore-activity, which was suggestive of reactive astrogliosis, was noted throughout the hippocampal subfields. Many degener-ating neurons were TUNEL positive. Electron microscopic findings revealed characteristic features of apoptosis in the dentate granule cells. NADPH-diaphorase positive cells were spared after TMT exposure. CONCLUSIONS: It is suggested that TMT-induced hippocampal degeneration might be a useful in vivo model for the study of learning and memory, neuronal-glial interactions, and selective neuronal apoptosis.
Aggression ; Apoptosis* ; Cell Death ; Dentate Gyrus ; Glial Fibrillary Acidic Protein ; Hippocampus ; In Situ Nick-End Labeling ; Learning ; Limbic System ; Memory ; Neurons ; Seizures ; Tremor

BACKGROUND: Trimethyltin (TMT) is a neurotoxicant which produces a distinct pattern of neuronal cell death in the hippocampus following systemic administration of a single dose. However, the mechanism of selective neuronal death remains unclear. We performed this study to elucidate the underlying mechanism of TMT-induced hippocampal neu-ronal death. METHODS: The effects of trimethyltin (8.0mg/kg, I.p., single dose) on the hippocampal neurons were investi-gated in terms of changes in the neurobehavioral status, histologic, and electron microscopc findings. RESULTS: Behaviorally, TMT treatment caused stereotypic limbic system dysfunction, i.e. tremors, spontaneous seizures, vocaliza-tion, hyperactivity, hyperexcitability, intraspecific aggression as described previously. Morphologically, TMT produced prominent neurodegeneration in the dentate gyrus. Widespread, strong glial fibrillary acidic protein (GFAP) immunore-activity, which was suggestive of reactive astrogliosis, was noted throughout the hippocampal subfields. Many degener-ating neurons were TUNEL positive. Electron microscopic findings revealed characteristic features of apoptosis in the dentate granule cells. NADPH-diaphorase positive cells were spared after TMT exposure. CONCLUSIONS: It is suggested that TMT-induced hippocampal degeneration might be a useful in vivo model for the study of learning and memory, neuronal-glial interactions, and selective neuronal apoptosis.
Aggression ; Apoptosis* ; Cell Death ; Dentate Gyrus ; Glial Fibrillary Acidic Protein ; Hippocampus ; In Situ Nick-End Labeling ; Learning ; Limbic System ; Memory ; Neurons ; Seizures ; Tremor

Vertebral artery dissection is one of the most common causes of stroke in young adults. The course of the vertebral artery dissection is usually benign, and pure transient amnesia as an initial symptom has been rarely reported. We describe a patient with vertebral artery dissection who presented with acute transient amnesia, and review the medical literatures about the pathophysiological mechanism of transient global amenesia (TGA). This case could be a one of evidence which supports the cerebrovascular mechanism of TGA.
Amnesia ; Amnesia, Transient Global* ; Humans ; Stroke ; Vertebral Artery Dissection* ; Young Adult