OBJECTIVE: This study was designed for developing a new experimental animal model of Wernicke's encephalopathy, and for investigating the timesequential morphological changes in the thiamine deficient rat brain by thiamine deficient diet with short term treatment of pyrithiamine. METHODS: A total of 40 healthy Sprague-Dawley strain rats, weighing about 2OOgm were used as experimental animals, divided into 10 control rats and 30 thiamine deficient experimental rats. Pyrithiamine (50mg/lOOgm/day) was injected intraperitonially for 9 days and thiamine deficient diet (20gm/rat/day) was continuously supplied until sacrifice. Then thiamine deficient experimental rats were subdivided into 3 groups according'to the exposure time of thiamine deficiency. For observing the morphological features in thalamus, medial mammillary nucleus and CA, sector in hippocampus, luxol-fast blue-cresy violet stain was performed. RESULTS: Treatment with pyrithiamine and thiamine deficient diet results in weight loss and decrement of body temperature on the 12th-14th day, followed by various neurologic manifestations, such as ataxia, hypotonia, circling movement, opisthotonus and loss of righting reflex, on the 16th-20th day, and then died on the 23th-25th, day. Chromatolysis and nuclear condensation of neurons in thalamus, medial mammillary nucleus and CA1 region of hippocampus are observed in group I. Mild edematous changes with neuronal necrosis in group II, and marked neuronal loss with severe edematous necrosis in group III are noted in same regions. CONCLUSION: These time sequential consistent morphological changes suggest that our experimental method could be used as a new animal model of Wernicke's encephalopathy in studying the sequential changes of thiamine deficient rat brain.
Animals ; Ataxia ; Body Temperature ; Brain ; Diet* ; Hippocampus ; Models, Animal ; Muscle Hypotonia ; Necrosis ; Neurologic Manifestations ; Neurons ; Prosencephalon* ; Pyrithiamine* ; Rats* ; Rats, Sprague-Dawley ; Reflex, Righting ; Thalamus ; Thiamine Deficiency ; Thiamine* ; Viola ; Weight Loss ; Wernicke Encephalopathy

Neuregulin-1 (NRG1) plays important roles in the development and plasticity of the brain, and has also been reported to exhibit potent neuroprotective properties. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its role in Alzheimer's disease (AD). AD is characterized by progressive impairment of cognition and behavioral disturbance that strongly correlate with degeneration and death of neurons in the cerebral cortex and limbic brain areas, such as the hippocampus and the amygdala. Here, we show that the ErbB4 and phospho-ErbB4 immunoreactivities were higher intensity in the neurons of the CA1-2 transitional field of AD brains as compared to age-matched controls. Also, ErbB4 expression was increased in the neurons of the cortico medial nucleus amygdala, human basal forebrain and superior frontal gyrus of AD brains. In cerebral cortex and hippocampus of amyloid precursor protein/presenilin 1 double transgenic mice, ErbB4 immunoreactivity significantly increased in comparison to age-matched wild type control. These results suggest that up-regulating of ErbB4 immunoreactivity may involve in the progression of pathology of AD.
Adult ; Alzheimer Disease ; Amygdala ; Amyloid ; Animals ; Brain ; Cerebral Cortex ; Cognition ; Hippocampus ; Humans ; Mice ; Mice, Transgenic ; Neuregulin-1 ; Neurons ; Plastics ; Prosencephalon

BACKGROUND: Diverse injury to central nervous system results in proliferation and hypertrophy of astrocytes. The hallmark of this response is enhanced expression of the major intermediate filament protein of astrocyte, glial fibrillary acidic protein(GFAP). These obsevations suggested that GFAP may be a useful biochemical indicator of neurotoxicity. This study is designed for investigating the chronological effects of the thiamine deficiency on the astrogrial GFAP immunoreactivity in the rat forebrain, and for comparing the difference between time-sequenital morphological changes of luxol fast blue-cresyl violet stain reported in previous study and GFAP immunoreactivity. METHODS: A total of 40 healthy Sprague-Dawley strain rats, weighing about 200gm were used as experimental animals(10 control, 30 thiamine deficient rats). Pyrithiamine was injected intraperitonially for 9 days and thiamine deficient diet was continuously supplied until sacrifice. Thiamine deficient rats were subdivided into 3 groups according to thiamine deficient state. Immunohistochemical stains for GFAP in the regions of thalamus, medial mammillary nucleus and CA1 sector in hippocampus were performed by free floating method in cell culture plate. All preperations were observed with light microscope. RESULTS: GFAP immunoactivities at thalamus were tracely positive(+) in controls, strongly positive(+++) in group I, and moderately positive(++) in group II and III. But GFAP immunoactivities at medial mammillary nucleus were tracely positive( ) in controls, moderately positive(++) in group I and III , and strongly positive(+++) in group II. At the CA1 region of hippocampus, the immunoactivities were weakly positive in controls , strongly positive(+++) in group I and II, and moderately positive(++) in group III. The diverse patterns of GFAP immunoreactivities in each vulnerable site were different from the previous morphological study. In luxol-fast and cresyl violet staining, the neuronal damage and necrosis were marked in group III, group II, and group I, in that order, which findings are consistent in all regions. CONCLUSIONS: Different patterns of time-sequential GFAP immunoactivities at each vulnerable site suggest that there are regional differences in sensitivity and resistance to thiamine deficiency.
Animals ; Astrocytes ; Cell Culture Techniques ; Central Nervous System ; Coloring Agents ; Diet ; Glial Fibrillary Acidic Protein* ; Hippocampus ; Hypertrophy ; Intermediate Filaments ; Necrosis ; Neurons ; Prosencephalon* ; Pyrithiamine ; Rats* ; Rats, Sprague-Dawley ; Thalamus ; Thiamine Deficiency* ; Thiamine* ; Viola

Neuregulin-1 (NRG1) signaling participates in the synaptic plasticity, maintenance or regulation of adult brain. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its localization in Alzheimer's disease (AD) brains. We previously reported that ErbB4 immunoreactivity showed regional difference in the hippocampus of age-matched control. In the present paper, immunohistochemical characterization of the distribution of ErbB4 receptor in the hippocampus relative to pathology staging were performed in age-matched control (Braak stage 0, n=6) and AD (Braak stage I/V, n=10). Here, we found that ErbB4 immunoreactivity was significantly increased in apoptotic hippocampal pyramidal neurons in the brains of AD patients, compared to those of age-matched control subjects. In AD brains, ErbB4 immunoreactivity was demonstrated to colocalize with the apoptotic signal Bax in apoptotic hippocampal pyramidal neurons. These results suggest that up-regulation of ErbB4 immunoreactivity in apoptotic neuron may involve in the progression of pathology of AD.
Adult ; Alzheimer Disease ; Animals ; Apoptosis ; Brain ; Hippocampus ; Humans ; Neuregulin-1 ; Neurons ; Plastics ; Up-Regulation

PURPOSE: To investigate the effect of dark rearing immediately after birth on the maturation of the visual relay neurons in the lateral geniculate nucleus. METHODS: Fifty neonatal rats were used. Neonates of the control groups were raised under a normal light/dark cycle. Neonates of the experiment groups were dark reared and isolated from light during the entire experimental period, then exposed to the sun light for 1 hour before sacrifice. RESULTS: In the control groups, the neurons in the dorsal lateral geniculate nucleus developed normally at each age tested. In the experiment groups, the cytoplasm of the large neurons in the dorsal lateral geniculate nucleus of 2-week-old rats contained small vesicles, and the cytoplasm of the large neurons of 4-week-old rats was converted into a vacuole-like space. Moreover, c-Fos immunoreactivity of the large neurons in the dorsal lateral geniculate nucleus in the experiment groups was significantly increased compared to that of the control groups. CONCLUSIONS: We suppose that the maturation of the neurons in the lateral geniculate nucleus might be influenced by light stimulation during the critical period. Furthermore, c-Fos could be a marker of the functional activity of the visual relay neurons of the lateral geniculate nucleus in albino rats.
Animals ; Animals, Newborn ; Critical Period (Psychology) ; *Dark Adaptation ; Geniculate Bodies/*metabolism ; Immunohistochemistry ; *Light ; Neurons/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley

Pulmonary surfactant prevents alveolar collapse by reducing alveolar surface tension and aids gaseous exchange in the lung. Since inadequate production of pulmonary surfactant is a key etiological process in ARDS, surfactant may play an important role in pathogenesis of ARDS. To provide a clue for establishing pathological mechanism of post-traumatic or neurogenic ARDS, we studied the influence of the vagal innervation on pulmonary surfactant metabolism. A total of 20 S-D rats (about 230 gm wt. each) were divided into two conditions: normal control and vagotomized groups. The vagotomized rats were subdivided into 3 hours, 8 hours and 24 hours groups. To preserve the superior cervical cardiac branches, both vagus nerves were cut at the lowest part of the carotid triangle. Cannula for adequate respiration and suction was fitted into the trachea. The lung tissue were processed for H&E, Masson's trichrome, Immunohistochemistry using anti-surfactant protein A (SP-A) and .anti-prosurfactant protein C (ProSP-C). The results were as follows; 1. The lungs of the vagotomized rats showed alveolar edema, fibrosis with infiltration of inflammatory cells and hyaline membrane formation. 2. In the lungs of the vagotomized rats, SP-A and ProSP-C immunoreactivity was decreased in proportion to postoperation time. Consequently, it can be postulated that autonomic disturbances caused by vagal interruption may induce ARDS-like pulmonary damage by modulating alveolar surfactant protein metabolism and by evoking the secondary inflammatory processes.
Animals ; Catheters ; Edema ; Fibrosis ; Hyalin ; Immunohistochemistry ; Lung ; Membranes ; Metabolism ; Protein C ; Pulmonary Surfactants ; Rats ; Respiration ; Staphylococcal Protein A ; Suction ; Surface Tension ; Trachea ; Vagotomy* ; Vagus Nerve

The ras-related GTP binding protein, rab6, is located in late Golgi compartment. Modulation of beta-and gamma-secretase activity may lead to production of beta-amyloid fragments that are ultimately deposited in senile plaques at the brain of Alzheimer patients. Because modulation of rab6-mediated intracellular transport has been known to affect amyloid precursor protein (APP) processing, we investigated the rab6 immunoreactivity on the hippocampal neurons in the Alzheimer brains, according to the pathological staging of the disease. A total of 30 brains were used for this study. Campbell's silver stain for beta-amyloid and immunohistochemistry for rab6 protein were employed. The cortices of the hippocampal formation and the neighboring temporal neocortex were observed. The results are obtained as follows: 1. In normal elderly brains, no amyloid plaque is seen. In Alzheimer brains, a number of amyloid plaques are seen at the temporal neocortex and dentate gyrus. 2. In normal elderly brains, the perikaria of the pyramidal cells at the CA1 sector shows weak rab6 immunoreactivity. At the CA2 and CA3 sectors, trace immunoreactivity is observed in the pyramidal cells. 3. In preclinical Alzheimer brains, the perikaria of the pyramidal cells at the CA1 sector shows moderate rab6 immunoreactivity and the cells at the CA2 sector show weak immunoreactivity. A weak to moderate imunoreactivity is seen in the pyramidal cells of the CA3 sector. 4. In clinical Alzheimer brains, the pyramidal cells at the CA1 and CA3 sectors show strong rab6 immunoreactivity, but the cells at the CA2 sector shows moderate immunoreactivity. It is suggested that alteration of intracellular protein transport caused by abnormal rab6 activity may modulate amyloid precursor protein processing, which results in beta-amyloid production.
Aged ; Amyloid ; Amyloid Precursor Protein Secretases ; Brain* ; Dentate Gyrus ; GTP-Binding Proteins ; Hippocampus ; Humans ; Immunohistochemistry ; Neocortex ; Neurons ; Plaque, Amyloid ; Protein Transport ; Pyramidal Cells ; Silver

During the routine gross anatomical dissection, bilateral absence of the musculocutaneous nerve and unilateral brachioradial artery were found in a 76-year-old Korean male cadaver. At the apex of the axilla, the lateral cord of the brachial plexus united into the median nerve without branching off the musculocutaneous nerve. The flexor arm musculatures, normally innervated by the musculocutaneous nerve, were innervated by two separate branches from the median nerve. The distal one continued as the lateral antebrachial cutaneous nerve. In addition, the radial artery of the left arm was originated from the middle one-third of the brachial artery. At bifurcation, it lay deep to the median nerve and crossed it medially. However, at the elbow, it crossed again the median nerve anterolaterally. Just above the cubital fossa, it anastomosed with the brachial artery. The arterial distribution of the right arm was normal. The separate reports which described the absence of the musculocutaneous nerve or brachioradial artery have been reported. However, this combined variation has not been documented until now.
Aged ; Arm ; Arteries ; Axilla ; Brachial Artery ; Brachial Plexus ; Cadaver ; Elbow ; Humans ; Male ; Median Nerve ; Musculocutaneous Nerve ; Radial Artery

Neuregulin-1 (NRG1) signaling participates in numerous neurodevelopmental processes. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its expression in aged human brain. We show that ErbB4 immunoreactivity was shown regional difference in the hippocampus of age-matched control and that the distribution of these molecules was altered in Alzheimer's disease (AD) brains. Immunohistochemical characterization of the distribution of ErbB4 receptor in the hippocampus relative to pathology staging were performed in age-matched control (Braak stage I/II, n=5), early AD (Braak stage III/IV, n=5) and advanced AD(Braak stage V/VI, n=10). The intensity of ErbB4 immunoreactivity was higher in neurons of the CA2 than that in CA1 or CA3 in the age-matched control. Particularly, in the early AD, ErbB4 immunoreactivity was significantly increased in the apoptotic cells of the CA2 field. In the advanced AD, ErbB4 immunostaining was more intense in the apoptotic cell of the CA2 field. In the dentate gyrus (DG), ErbB4-positive granular cell density was gradually increased in proportion to the progression of pathology of AD brains. We have also found that ErbB4 immunostaining was increased in the nucleus, suggesting that the presenilin-dependent cleavage of ErbB4 generates the soluble ErbB4 ICD (intracellular domain) that translocalized to the nucleus. Together, these results provide the immunohistochemical analysis of ErbB4 receptor in the human hippocampus staged by the progression of pathology of AD.
Adult ; Aged ; Alzheimer Disease ; Animals ; Apoptosis ; Brain ; Cell Count ; Dentate Gyrus ; Hippocampus ; Humans ; Neuregulin-1 ; Neurons

It has been demonstrated that some of immediate early genes (IEGs) such as c-Jun or fos are induced immediately following neuronal injury and they play an important role in determining the fate of the injured neurons. Of IEGs, the activating transcription factor 3 (ATF3) is focused by many investigators, because they are expressed in various types of neural insults and have been known to serve a diverse function in both neuronal survival and death. However, little is known about the functional role of ATF3 in ischemic brain injury. So in this study, the authors examined the expression pattern of the activating transcription factor 3 (ATF3) following middle cerebral artery (MCA) occlusion-reperfusion injury. According to the findings obtained by triphenyltetrazolium chloride (TTC) stains, the authors have classified the infarcted area into two regions, the ischemic core region and the ischemic penumbra region. In both regions, many neurons underwent neuronal degeneration, characterized by the shrunken nuclei with eosinophilic perikaryon. The H & E stain also demonstrated the increased number of probable activated astrocytes and microglia in the ischemic brain regions and this was confirmed by GFAP- and OX42-immunohistochemistry. Immunohistochemical study for ATF3 also demonstrated the specific upregulation of ATF3 in the nuclei of neurons under ischemic injury, but not in those of the contralateral regions. Interestingly, the number of the ATF3 positive neurons in the ischemic penumbra regions outnumbered that of the ischemic core regions. Based on many reports that the neuronal death in ischemic penumbra region is caused by programed cell death rather than by necrosis which is main cause of neuronal death in ischemic core region, our results could suggest that the ATF3 is an important IEGs which determine the fate of the ischemic neurons.
Activating Transcription Factor 3 ; Astrocytes ; Brain ; Brain Injuries ; Brain Ischemia ; Cell Death ; Coloring Agents ; Eosinophils ; Genes, Immediate-Early ; Humans ; Microglia ; Middle Cerebral Artery ; Necrosis ; Neurons ; Research Personnel ; Tetrazolium Salts ; Up-Regulation