Chronic treatment of haloperidol induces pathological changes in striatal neurons of guinea pigs: a light and electron microscopical study.

In the present work, we investigated whether there would be any change in histological structure of striatal neurons after haloperidol applications at different doses. Adult male guinea pigs were treated once-daily with saline (group 4, control) or haloperidol during 6 weeks, and the dose was 1, 2, or 3 mg/kg (groups 1, 2, and 3, respectively). After treatment, all animals were anesthetized and striata were dissected and examined. When striata were evaluated histologically, dark neurons and some degenerating striatal neurons had distinctive morphological changes consistent with cell death, including reduced neuronal size with nuclear and cytoplasmic shrinkage. Also, in sections of striata in groups 1 and 2, but not in group 3, more glial cells were observed than in those of the control group. In all treated groups, fibrous content of intersititium was paralelly increased by increasing dose. Ultrastructural investigation of striatal neurons in haloperidol-treated rats showed notched nuclei and many lysosomes. Moreover, degeneration of myelin, scarce microglial macrophages, expansion of nuclear intermembranous space, degenerated mitochondria, and vacuoles were found. Also, cytoplasmic swelling, lysosomes, and apoptotic bodies were present. These results suggest that haloperidol treatment may lead to damage in neurons via the necrotic process in both low- and high-dose applications.

Effect of high fat diet on the volume of liver and quantitative feature of Kupffer cells in the female rat: a stereological and ultrastructural study.

BACKGROUND: The role of Kupffer cells (KCs) in nonalcoholic steatohepatitis (NASH) which is regarded as a major cause of cryptogenic cirrhosis of the liver was investigated using stereological methods and electron microscopy in the rat model. To our knowledge, there is no stereological study on the volume of liver, total number, numerical density, and nuclear height of KCs of liver in the female rat fed with a high fat diet (HFD) in the literature. METHOD: 16 female Sprague Dawley rats were randomized into HFD and control group, with HFD and standard diet for 12 weeks, respectively. In this study, two basic research methods were used to analyze the samples. One was histopathological observation at both light and electron microscopic level. The other was stereological methods that consist of Cavalieri principle for liver volume estimation and physical disector method for estimation of numerical density and total number of KCs in the liver. RESULTS: Liver volume, both mean numerical density and total number of KCs, were statistically increased in HFD rats. Ultrastructurally, a significant decrease in the mean nuclear height of KCs in HFD rats was also found. In the control group, no abnormal change was observed, but in the HFD group, some changes such as diffuse steatosis, mononuclear cell infiltration, necrosis, fibrosis, accumulation of fat droplets and intra-cytoplasmic vacuoles, and swollen mitochondria with irregular membranes were observed in the hepatocytes. CONCLUSION: The number and activity of KCs are increased significantly in NASH induced by HFD, and KCs might be involved in the pathogenesis of steatohepatitis as previously attributed as a major cause of cryptogenic cirrhosis of the liver.

Effect of a high fat diet on quantitative features of adipocytes in the omentum: an experimental, stereological and ultrastructural study.

BACKGROUND: Omental adipose tissue specimens of female rats that were fed a high fat (HF) diet were evaluated stereologically and histopathologically. To our knowledge, there is no stereological study on numerical density, nuclear height and volume of adipocytes in omental adipose tissue in the female rat fed a HF diet in the literature. METHOD: 20 female Spraque Dawley rats were used in the study. 10 of the animals were fed HF diet consisting of 30% of calories from fat for 3 months. The remaining 10 rats, the control group, were fed a normal diet. After the experimental procedure, all animals were anesthetized and omental adipose tissues in the same area were dissected and fixed for the histochemical process using a mixture of 3% glutaraldehyde and 1% osmium tetraoxide in 0.1 M phosphate buffer. After embedding of tissues in araldite CY 212, semi-thin and thin sections were cut. The semi-thin sections were stained with toluidine blue. The physical dissector counting method was used for estimation of numerical density and nuclear height of adipocytes. Cavalieri principle was used for the estimation of adipocyte volume; volume fraction approach was applied to find the volume fraction of adipose tissue components. RESULTS: The mean numerical density of adipocytes in the HF diet group was significantly higher than the control. The mean nuclear height of adipocytes was also very high in the HF diet group. The volume fraction of adipose mass was increased whereas the extracellular matrix volume fraction was reduced in the HF diet group compared to the controls. The mean volume of adipocytes in the HF diet group was also significantly higher than in the control group. At the light microscopy level, it was found that adipocytes were enlarged and gaining irregular shape in the HF diet group. Thicker basal lamina and electron dense lipid content were also found in this group at the electron microscopy level. CONCLUSION: Lipid content and number of adipocytes in the adipose tissue of HF diet rats were higher than in the controls. Thus, HF diet induces increase in body weight via both hypertrophy and hyperplasia of adipocytes.

The influence of cigarette smoke on the epithelium of the vestibule: an electron microscopic study.

It is known that cigarette smoke induces cytological alterations on the respiratory and olfactory mucosa of the nasal cavity. We evaluated whether cigarette smoking had adverse effects on the epithelium of the vestibule, in the absence of any published ultrasutructural studies. We evaluated ten patients suffering from septum deviation, eight of whom were long-term smokers. While each layer of the epithelium obtained from the non-smokers consisted of a homogeneous cell population, each from the long-term smokers consisted of a heterogeneous cell population. The most prominent changes occurred in the shape and size of the cells and nuclei, the number and length of the cytoplasmic projections, the number and distribution pattern of the desmosomes, and the width of the intercellular spaces. We concluded that cigarette smoke produces hyperplastic and dysplastic changes, important factors related with cancer development, on the epithelium of the vestibule.

Effects of haloperidol on striatal neurons: relation to neuronal loss (a stereological study).

In the present work, we investigated the effect of chronic haloperidol administration on the number of striatal neurons in guinea pigs. For this purpose, adult male guinea pigs were given daily injections of 1, 2 or 3 mg/kg of haloperidol for 6 weeks. After treatment, the animals were anesthetized via brief inhalation of ether, the brains were removed and the corpus striatum was dissected. Then the tissues were processed and semi-thin sections were stained with toluidine blue for stereological and histopathological evaluation. The physical disector was used for measurements of nuclear height and numerical density of striatal neurons and also to evaluate both normal and degenerated neurons within the corpus striatum of treated animals and untreated controls. In the control group, the mean numerical density of neurons was calculated as 47.92 cell/mm3 and the mean nuclear height as 3.58 µm. Mean densities of all (both viable and degenerated) neurons were calculated to be 45.46 in the low-dose (p < 0.01), 39.73 in the medium-dose (p < 0.001) and 30.31 cell/mm3 in the high-dose group (p < 0.001). Mean densities of degenerated neurons in the low, medium and high dose group were 30.72, 22.93 (p < 0.001) and 15.56 cell/mm3 (p < 0.001) respectively. Mean nuclear heights were 2.804 (p < 0.0001), 2.78 (p < 0.0001) and 2.33 µm (p < 0.00001) in the low, medium and high dose group, respectively.