scholarly journals Heat Acclimation Regulates the Autophagy-Lysosome Function to Protect Against Heat Stroke-Induced Brain Injury in Mice

2017 ◽  
Vol 41 (1) ◽  
pp. 101-114 ◽  
Author(s):  
Junfeng Yi ◽  
Genlin He ◽  
Ju Yang ◽  
Zhen Luo ◽  
Xuesen Yang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neuroprotective Effect ◽  
Heat Stroke ◽  
Microscopic Analysis ◽  
Heat Acclimation ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Autophagic Flux ◽  
Protective Effects ◽  
Electron Microscopic ◽  
Fluoro Jade B

Background/Aims: The mechanisms underlying the protective role of heat acclimation (HA) in heat stroke (HS)-induced brain injury are still unclear. The autophagy-lysosome pathway is known to pay an important role in protecting stressed or diseased cells from death. Nevertheless, whether autophagy and lysosomes are involved in HA-mediated neuroprotection following HS exposure remains unclear. Methods: The protective effects of HA were assessed by rectal temperature, hematoxylin-eosin staining, transmission electron microscopic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Fluoro Jade B staining, after mice were subjected to HS. The effects of HA on autophagy and lysosomes were assessed in the presence of the autophagy inhibitor 3-methyladenine (3MA). Autophagy and lysosome-associated proteins were analysed by Western blotting. Results: We found that HA protected against HS-induced death and brain injury. HS can robustly induce autophagy and impair lysosome function. HA pre-conditioning significantly modulated the autophagy level, and improved lysosome function in HS mice. Furthermore, 3MA completely abolished the neuroprotective effect of HA on HS. Conclusion: HS may induce brain injury through lysosomal dysfunction and impaired autophagic flux. HA protected against HS-induced brain injury via a mechanism involving the autophagy-lysosome pathway.

scholarly journals Effect of curcumin in the acute phase of ischemia in chronic cerebral hypoperfusion in rats

2018 ◽  
Vol 17 (1) ◽  
pp. 69-73
Author(s):  
N. S. Shcherbak ◽  
M. A. Popovetskiy ◽  
G. Yu. Yukina ◽  
M. M. Galagudza
Keyword(s):  
Brain Injury ◽  
Acute Phase ◽  
Wistar Rats ◽  
Neuroprotective Effect ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ischemic Brain Injury ◽  
Protective Effects ◽  
Single Application ◽  
Ischemic Brain

Curcumin presents antioxidant and anti-inflammatory properties and can be considered as a neuroprotector. Data on doses and duration of application of curcumin to achieve protective effects in various types of ischemic brain injury is controversial. The purpose was to study the neuroprotective properties of curcumin in the acute phase of ischemia in chronic cerebral hypoperfusion in rats. It is shown that a single application of curcumin (300 mg/kg, i.p.) is not has neuroprotective effect in the acute phase of ischemia in chronic hypoperfusion in Wistar rats. The results allow to conclude that the neuroprotective effect of a single application of curcumin.

Evaluation of the Neuroprotective Effect of Pycnogenol in a Hypoxic-Ischemic Brain Injury Model in Newborn Rats

2021 ◽  
Author(s):  
Ruya Çolak ◽  
Aslı Celik ◽  
Gulden Diniz ◽  
Senem Alkan Özdemir ◽  
Osman Yilmaz ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cell Injury ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Albino Rats ◽  
Protective Agent ◽  
Injury Model ◽  
Group B ◽  
Factor Α

Objective This study aimed to evaluate the efficacy of Pycnogenol (PYC) and its antioxidant and antiapoptotic effect in an experimental hypoxic-ischemic (HI) rat model. Study Design A total of 24 Wistar albino rats who were on the seventh postnatal day were divided into three groups with developed HI brain injury model under the sevoflurane anesthesia: 40 mg/kg PYC was given to Group A, saline was given to Group B, and the sham group was Group C. Neuronal apoptosis was investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemically stained manually with primer antibodies of tumor necrosis factor-α and interleukin-1β. Results The neuronal cell injury was statistically lower in the PYC treatment group. Conclusion This is the first study that investigates the role of PYC in the HI brain injury model. PYC reduces apoptosis and neuronal injury in the cerebral tissue of the rats. PYC may be a protective agent against hypoxic-ischemic encephalopathy. Key Points

Melatonin preserves ovarian tissues of rats exposed to chronic TCDD: An electron microscopic approach to effects of TCDD on ovarian cells

2018 ◽  
Vol 34 (4) ◽  
pp. 228-236 ◽  
Author(s):  
Semir Gül ◽  
Mehmet Gül ◽  
Birgül Yigitcan
Keyword(s):  
Hormonal Regulation ◽  
Microscopic Analysis ◽  
The Body ◽  
Female Rats ◽  
Control Group ◽  
Corpora Lutea ◽  
Protective Effects ◽  
Electron Microscopic ◽  
Toxic Agent ◽  
Ameliorative Effect

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is a toxic agent and has disruptive effects on reproductive tissues in females. TCDD disrupts the hormonal regulation of the body and decreases the production of melatonin. In this study, we investigated the protective effects of melatonin supplements against the toxic effects of TCDD on ovaries of female rats. TCDD caused a significant decrease in the average number of corpora lutea and follicles per tissue section (2.1 ± 0.7; 2.3 ± 0.8, respectively), whereas these numbers were maintained in the melatonin supplemented group (5.0 ± 0.8; 5.1 ± 0.8, respectively) and were similar to the control group (5.3 ± 1.0; 5.9 ± 0.9, respectively). Electron microscopic analysis showed that the disruption of ultrastructure components such as cell membrane and organelles due to TCDD exposure was inhibited by melatonin supplements. This study suggested that melatonin has a protective and a possible ameliorative effect over histopathological damage of rat ovaries exposed to TCDD.

Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice

2017 ◽  
Vol 95 (12) ◽  
pp. 1396-1405 ◽  
Author(s):  
Mei-li Ding ◽  
Hui Ma ◽  
Yi-gang Man ◽  
Hong-yan LV
Keyword(s):  
Learning And Memory ◽  
Green Tea ◽  
Survivin Expression ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Mrna Levels ◽  
Protective Effects ◽  
Neonatal Mice ◽  
Fluoro Jade B ◽  
Green Tea Polyphenol ◽  
Gsk 3Β

Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7. EGCG significantly inhibited sevoflurane-induced neuroapoptosis as determined by Fluoro-Jade B staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Increased levels of cleaved caspase-3, downregulated Bad and Bax, and significantly enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, and survivin expression were observed. EGCG induced activation of the PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3β, phospho-GSK-3β, and mTORc1 levels. Sevoflurane-mediated downregulation of cAMP/CREB and BDNF/TrkB signalling was inhibited by EGCG. Reverse transcription PCR analysis revealed enhanced BDNF and TrkB mRNA levels upon EGCG administration. Improved performance of mice in Morris water maze tests suggested enhanced learning and memory. The study indicates that EGCG was able to effectively inhibit sevoflurane-induced neurodegeneration and improve learning and memory retention of mice via activation of CREB/BDNF/TrkB–PI3K/Akt signalling.

scholarly journals Induction of the Vitamin D Receptor Attenuates Autophagy Dysfunction-Mediated Cell Death Following Traumatic Brain Injury

2017 ◽  
Vol 42 (5) ◽  
pp. 1888-1896 ◽  
Author(s):  
Changmeng Cui ◽  
Jianzhong Cui ◽  
Feng Jin ◽  
Ying Cui ◽  
Ran Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Vitamin D ◽  
Cell Death ◽  
Brain Injury ◽  
Protein Expression ◽  
Rat Brain ◽  
Male Rats ◽  
Autophagic Flux ◽  
Sham Operation ◽  
Protective Effects

Background/Aims: Traumatic brain injury (TBI) is a major public health problem in the world and causes high rates of mortality and disability. Recent evidence suggests that vitamin D (VD) has neuroprotective actions and can promote function recovery after TBI. In vitro and in vivo studies have demonstrated that autophagy could be enhanced following supplementation with an active metabolite of VD (calcitriol). However, it is unclear whether autophagy participates in the protective effects of calcitriol after TBI. To test this hypothesis, we examined the protective effects of calcitriol on TBI-induced neurological impairment and further investigated whether calcitriol could modulate autophagy dysfunction-mediated cell death in the cortex region of rat brain. Methods: Eighty-five male rats (250-280 g) were randomly assigned to sham (n=15), TBI model (TBI, n=35) and calcitriol treatment (calcitriol, n=35) groups. Rats were injected intraperitoneally with calcitriol (1 µg/kg) at 30 min, 24 h and 48 h post-TBI in the calcitriol group. The lysosomal inhibitor, chloroquine (CQ), was used to evaluate autophagic flux in the TBI and calcitriol groups. Neurological functions were evaluated via the modified neurological severity score test at 1-7 days after TBI or sham operation, and the terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick-end labeling method was used to evaluate the ability of calcitriol to inhibit apoptosis. The expression of VDR, LC3 and p62 proteins was measured by western blot analysis at 1, 3 and 7 days post-injury Results: Calcitriol treatment attenuated mNSS at 2-7 days post-TBI (P < 0.05 versus TBI group). Calcitriol dramatically increased VDR protein expression compared with the untreated counterparts at 1, 3 and 7 days post-TBI (P < 0.05). The rate of apoptotic cells in calcitriol-treated rats was significantly reduced compared to that observed in the TBI group (P < 0.05). The LC3II/LC3I ratio was decreased in the cortex region at 1, 3 and 7 days post-TBI in rats treated with calcitriol (p < 0.05 versus TBI group), and the p62 expression was also attenuated (p < 0.05 versus TBI group). The LC3II/LC3I ratio in the calcitriol group was significantly increased when pretreated with CQ (P < 0.05). Conclusion: Calcitriol treatment activated VDR protein expression and attenuated neurological deficits in this rat TBI model. The protective effects might be associated with the restoration of autophagy flux and the decrease in apoptosis in the cortex region of rat brain.

scholarly journals Morphological Aspects of the Postnatal Development of Submandibular Glands in Male Rats: Involvement of Apoptosis

2000 ◽  
Vol 48 (5) ◽  
pp. 695-698 ◽  
Author(s):  
Hiroyuki Hayashi ◽  
Satoru Ozono ◽  
Kazuko Watanabe ◽  
Nagatsu Ikuko ◽  
Minoru Onozuka
Keyword(s):  
Postnatal Development ◽  
Submandibular Gland ◽  
Light And Electron Microscopy ◽  
Microscopic Analysis ◽  
Male Rats ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Male Rat ◽  
Electron Microscopic ◽  
Morphological Aspects ◽  
Tubule Cells

SUMMARY We studied the involvement of the apoptotic mechanism(s) in cell differentiation in the developing male rat submandibular gland using the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-labeling) assay in combination with light and electron microscopy. Whereas the proacinar cells were completely transformed into acinar cells within 2 weeks after birth, starting on postnatal Day 21, the terminal tubule cells formed vacuoles that disappeared by postnatal Day 35. During this period, positive TUNEL reactivity was seen in the terminal tubule cells, and electron microscopic analysis showed that certain morphological features of apoptosis, including fragmentation of nuclei and the presence of apoptotic bodies in the cytoplasm, were present in and restricted to the terminal tubule cells. These results indicate that, in addition to an autophagocytosis-mediated mechanism, apoptosis may also be involved in reducing the number of terminal tubule cells during postnatal development in the submandibular gland.

scholarly journals ATF4 promotes renal tubulointerstitial fibrosis by suppressing autophagy in diabetic nephropathy

2020 ◽  
Author(s):  
Qiuer Liang ◽  
Tianhao Liu ◽  
Tingting Guo ◽  
Wencong Tao ◽  
Xudong Chen ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Western Blot ◽  
High Glucose ◽  
Microscopic Analysis ◽  
Tubulointerstitial Fibrosis ◽  
Autophagic Flux ◽  
Electron Microscopic ◽  
Renal Tubulointerstitial Fibrosis ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Diabetic nephropathy (DN) is the dominant cause of end-stage renal disease which is characterized by extracellular matrix accumulation. The purpose of this study was to investigate the role of activating transcription factor 4 (ATF4) in regulating renal fibrosis and autophagy in DN. Methods Streptozotocin (STZ) was administered to heterozygous ATF4 knockout (KO) and wild-type (WT) mice via an intraperitoneal injection to induce DN. NRK-52E cells were cultured in high glucose to mimic diabetic pathological. qRT-PCR, western blot, immunofluorescence, histology and electron microscopic analysis were performed. The autophagy flow was observed by tandem mRFP-GFP-LC3 fluorescence microscopy. Results DN mice experienced severe renal injury and fibrosis and showed increased expression of ATF4 and inhibition of autophagy in kidney tissues. STZ-induced ATF4 KO mice showed significant improvement in urinary albumin, serum creatinine and blood urea nitrogen and the pathological changes of renal tubulointerstitial fibrosis compared with STZ-induced WT mice. Furthermore, western blot assays and immunofluorescence staining revealed that inhibition of ATF4 could restore autophagy in DN mice. Overexpression of ATF4 in NRK-52E cells cultured in high glucose condition suppressed autophagy and upregulated Col-IV expression, while inhibition of ATF4 could increase the number of the autophagosomes, improve autophagic flux and decrease Col-IV level. Conclusion Our study provided the first evidence of a crucial role for ATF4 in inhibiting autophagy against diabetic kidney damage. Suppression of ATF4 may be an effective therapy in restraining renal tubulointerstitial fibrosis in DN.

Apoptosis precedes necrosis of dystrophin-deficient muscle

1995 ◽  
Vol 108 (6) ◽  
pp. 2197-2204 ◽  
Author(s):  
J.G. Tidball ◽  
D.E. Albrecht ◽  
B.E. Lokensgard ◽  
M.J. Spencer
Keyword(s):  
Structural Changes ◽  
Muscle Fibers ◽  
Microscopic Analysis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Mdx Mice ◽  
Current View ◽  
Electron Microscopic ◽  
Preferential Cleavage ◽  
Tissue Sections ◽  
Necrotic Change

The current view that death of dystrophin-deficient muscle fibers is a necrotic process relies primarily upon the histological appearance of the tissue after the degenerative process is well advanced. Here, we tested this view by examining the possibility that apoptosis is a component of dystrophin-deficient muscle cell death. Three assays for apoptosis were employed in analyzing prenecrotic, peak necrotic and regenerated hindlimb muscle of mdx mice: (1) terminal deoxynucleotidyl transferase (TdT) mediated end-labeling of DNA in nuclei in tissue sections; (2) assays for DNA ladders; and (3) electron microscopic assays for the presence of organelles undergoing structural changes characteristic of apoptosis. At all ages sampled, mdx muscle contained apoptotic nuclei, according to TdT-mediated dUTP labeling of tissue sections. Nuclei in regenerated mdx muscle fibers did not display apoptosis. dUTP-labeled nuclei in control C57 muscles were rare or absent at all ages sampled. DNA from 4-week-old mdx mice was found to be cleaved into fragments indicative of preferential cleavage at internucleosomal sites. Electron microscopic analysis showed that organelle structural changes indicating apoptosis appear before pathological changes diagnostic of necrosis. For example, condensed mitochondria, fragmented sarcoplasmic reticulum and nuclei with chromatin condensations resembling apoptosis appear in fibers that otherwise possess normal morphology. Together, the findings show that apoptosis precedes any detectable necrotic change in mdx muscle, and that apoptotic events continue into the stage of dystrophic pathology that is currently viewed as necrosis. Thus, apoptosis characterizes the onset of pathology in dystrophin-deficient muscle which is followed secondarily by necrotic processes.

Preparatory Procedures for Electron Microscopic Analysis at the Molecular Level of Resolution

1978 ◽  
Vol 36 (3) ◽  
pp. 516-520
Author(s):  
F.J. Sjostrand
Keyword(s):  
Electron Microscope ◽  
Molecular Level ◽  
Microscopic Analysis ◽  
Resolving Power ◽  
Cellular Structures ◽  
Electron Microscopic ◽  
Systematic Analysis ◽  
Technical Developments ◽  
Thin Sectioning ◽  
Obvious Reason

In the 1940's and 1950's electron microscopy conferences were attended with everybody interested in learning about the latest technical developments for one very obvious reason. There was the electron microscope with its outstanding performance but nobody could make very much use of it because we were lacking proper techniques to prepare biological specimens. The development of the thin sectioning technique with its perfectioning in 1952 changed the situation and systematic analysis of the structure of cells could now be pursued. Since then electron microscopists have in general become satisfied with the level of resolution at which cellular structures can be analyzed when applying this technique. There has been little interest in trying to push the limit of resolution closer to that determined by the resolving power of the electron microscope.

Electron Microscopic identification of Pre-B Lymphocytes in the Bone Marrow of a Patient with Chronic Myelocytic Leukemic in Blast Crisis

1982 ◽  
Vol 40 ◽  
pp. 346-347
Author(s):  
T. Mullin ◽  
G. Yee ◽  
M. Aheam ◽  
J. Trujillo
Keyword(s):  
Blast Crisis ◽  
Immunoglobulin M ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Transformation Theory ◽  
Electron Microscopic ◽  
Chemotherapeutic Sensitivity ◽  
Microscopic Studies ◽  
Hematopoietic Precursor ◽  
Lymphoblastic Transformation ◽  
B Lineage

There have been numerous reports in the current literature suggesting that hematopoietic precursor cells in some human chronic myelocytic leukemias (CML) undergo lymphoblastic transformation at the time of the acute blast crisis (BC) stage. The primary evidence offered in support of this transformation theory--lymphoblastic appearing morphology, increased terminal deoxynucleotidyl transferase (TdT) activity, and chemotherapeutic sensitivity to vincristine and prednisone--has been indirect, however, since these features may occur in nonlymphoid cells. More direct support for the Pre-B lineage of these cells has recently been provided by immunofluorescent light microscopic studies demonstrating the presence of intracytoplasmic immunoglobulin M (IgM) in these CML-BC cells.

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