7 research outputs found
Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats
Get PDFParkinson's disease (PD) is the second most common neurodegenerative disorder affecting millions of people worldwide. At present, there is no effective cure for PD; treatments are symptomatic and do not halt progression of neurodegeneration. Extracellular vesicles (EVs) can cross the bloodābrain barrier and represent promising alternative to the classical treatment strategies. In the present study, we examined therapeutic effects of intranasal administration of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on unilateral 6āhydroxydopamine (6āOHDA) medial forebrain bundle (MFB) rat model of PD. CatWalk gait tests revealed that EVs effectively suppressed 6āOHDAāinduced gait impairments. All tested gait parameters (stand, stride length, step cycle, and duty cycle) were significantly improved in EVātreated animals when compared with 6āOHDAālesion group rats. Furthermore, EVs slowed down numbers of 6āOHDAāinduced contralateral rotations in apomorphine test. Improvements in motor function correlated with normalization of tyrosine hydroxylase expression in the striatum and substantia nigra. In conclusion, we demonstrated, for the first time, the therapeutic efficacy of intranasal administration of EVs derived from SHEDs in a rat model of PD induced by 6āOHDA intraāMFB lesion. Our findings could be potentially exploited for the development of new treatment strategies against PD
Jaunas farmakoterapeitiskas pieejas, kas mÄrÄ·Ätas uz neirodeÄ£eneratÄ«vajiem procesiem
No full textVisizplatÄ«tÄkÄs neirodeÄ£eneratÄ«vÄs un joprojÄm neizÄrstÄjamÄs slimÄ«bas ir sporÄdiskÄs formas Alcheimera slimÄ«ba (sAD) un PÄrkinsona slimÄ«ba (PD). TÄm ir kopÄ«gi etiopatoÄ£enÄtiski cÄloÅi, kas ar laiku izraisa kognitÄ«vo spÄju samazinÄÅ”anos. Terapija jÄmÄrÄ·Ä uz tiem patoloÄ£iskajiem procesiem, kas ir kopÄ«gi un raksturÄ«gi gan sAD, gan PD to agrÄ«najÄs stadijÄs. DarbÄ esam izvÄlÄjuÅ”ies inovatÄ«vu pieeju, izmantojot ekstracelulÄrÄs vezÄ«kulas (EVs) un antihiperglikÄmisko preparÄtu metformÄ«nu. IegÅ«tie dati pirmoreiz parÄda EVs un metformÄ«na neiroprotektÄ«vÄs un regulÄjoÅ”Äs Ä«paŔības sAD un PD modeļdzÄ«vniekos, kas norÄda uz Å”o vielu perspektivitÄti Å”o slimÄ«bu agrÄ«no stadiju patoloÄ£isko procesu savlaicÄ«gÄ apturÄÅ”anÄ. AtslÄgas vÄrdi: Alcheimera slimÄ«ba; PÄrkinsona slimÄ«ba; STZ; 6-OHDA; ekstracelulÄrÄs vezÄ«kulas; metformÄ«ns; gaita; mÄcÄ«Å”anÄs/atmiÅa; proteÄ«nu ekspresija.Sporadic Alzheimer's disease (sAD) and Parkinson's disease (PD) are the most common incurable neurodegenerative diseases. The diseases share common etiopathogenetic causes, that evoke cognitive impairment over time. Therapy must be aimed at pathogenetic processes, which are common and characteristic during the early stages of both sAD and PD. We have chosen an innovative approach, using extracellular vesicles (EVs) and anti-hyperglycemic drug metformin. The data obtained demonstrate, for the first time, neuroprotective and neuroregulatory properties of metformin and EVs in animal models, highlighting the usefulness of these substances in halting early pathological processes of sAD and PD. Key words: Alzheimer's disease; Parkinson's disease; STZ; 6-OHDA; extracellular vesicles; metformin; gait; spatial learning/memory; protein expressio
The alterations of Neuroinflammation expression in streptozotocin induced Alzheimers model in rats with muscimol
No full textAlcheimera slimÄ«ba ir biežÄkÄ neirodeÄ£eneratÄ«vÄ slimÄ«ba mÅ«sdienu sabiedrÄ«bÄ, ar tendenci slimnieku skaitam ar katru gadu pieaugt. SarežģītÄs diagnostikas un neefektÄ«vÄs farmakoloÄ£iskÄs terapijas dÄļ, Å”o slimÄ«bu ir grÅ«ti kontrolÄt. PÄtnieki nodarbojas ar Alcheimera slimÄ«bas pirms-demences diagnostikas metožu un veiksmÄ«gas farmakoloÄ£iskÄs terapijas atklÄÅ”anu. Balstoties uz iepriekÅ” veiktiem pÄtÄ«jumiem par GABAA agonista muscimola (0,01 un 0,05 mg/kg) spÄju samazinÄt neiroiekaisumu, streptozocÄ«na (STZ) izraisÄ«tÄ Alcheimera slimÄ«bas modelÄ« žurkÄm [MareÅ” P., et al. 2014], [Ding Y., et al. 2015], Å”ajÄ pÄtÄ«jumÄ tika apskatÄ«ta un analizÄta neiroiekaisuma biomarÄ·ieru ekspresija post mortem žurku smadzenÄs. Darba mÄrÄ·is bija noteikt muscimola ļoti mazo devu (0,01 un 0,05 mg/kg) efektu uz iekaisuma marÄ·ieriem: astroglijas specifisku (glial fibrillary acid protein, GFAP), mikroglijas specifisku (ionized calcium binding adaptor molecule 1, Iba-1) un dopamÄ«nerÄ£iskÄs sistÄmas specifisku tirozÄ«na hidroksilÄzes (TH) ekspresiju smadzeÅu struktÅ«rÄs garozÄ un hipokampÄ Alcheimera slimÄ«bas modelÄ« žurkÄm, kas radÄ«ts ar toksÄ«nu streptozocÄ«nu. Divas nedÄļas pÄc STZ vai mÄkslÄ«gÄ cerebrospinÄlÄ Å”Ä·idruma (aCSF) i.c.v. ievadÄ«Å”anas, pieauguÅ”iem dzÄ«vniekiem tika veikts Morisa Å«dens labirinta tests (Morris water maze), lai pÄrbaudÄ«tu telpisko atmiÅu un uzvedÄ«bu stresa apstÄkļos. PÄc tam tika ievÄktas dzÄ«vnieku smadzenes un, izmantojot imunohistoÄ·Ä«mijas analÄ«zi, pÄtÄ«tas minÄto marÄ·ieru ekspresijas izmaiÅas dažÄdos smadzeÅu reÄ£ionos. RezultÄti uzrÄdÄ«ja GFAP ekspresijas palielinÄjumu STZ grupÄ salÄ«dzimÄjumÄ ar kontroli. SAL+aCSF un muscimola abÄs devÄs redzams samazinÄjums GFAP ekspresijÄ salÄ«dzinÄjumÄ ar STZ grupu. Iba-1 marÄ·iera ekspresijai bija tendence samazinÄties M0,05-STZ grupÄ gan garozÄ, gan hipokampÄ, un TH marÄ·iera ekspresijas izmaiÅas tika novÄrotas garozÄ M0,01-STZ grupÄ. Muscimolam piemÄ«t spÄja mazinÄt iekaisumu, ko izraisÄ«jis streptozocÄ«ns un ir nepiecieÅ”ami tÄlÄki pÄtÄ«jumi, lai noskaidrotu darbÄ«bas mehÄnismu.Alzheimerās disease is the most common neurodegenerative disorder in modern society, and the number of patients tends to increase every year. It is difficult to control the disease because of complicated diagnostics and ineffective pharmacological therapy. Scientists are working on finding diagnostic techniques for Alzheimerās disease at pre-dementia stage and effective pharmacological therapy. Based on the previous studies about the low doses of GABAA agonist muscimolās ability (0.01 and 0.05 mg/kg) to reduce neuroinflammation in a streptozocin (STZ) induced rat model of Alzheimerās disease [Mares P., et al. 2014], [Ding Y., et al. 2015], the expression of the neuroinflammatory biomarkers was investigated and analyzed in post mortem rat brain. The goal of the MA thesis was to determine the effect of muscimol in low doses (0.01 and 0.05 mg/kg) on the particular neuroinflammatory biomarkers: astroglial-specific (glial fibrillary acid protein, GFAP), microglial-specific (ionized calcium binding adaptor molecule 1, Iba-1), and the specific expression of dopaminergic systemās tyrosine hydroxylase (TH) in the cerebral cortex and hippocampus of the streptozocin (STZ) induced rat model of Alzheimerās disease. Two weeks after the i.c.v. injection of STZ or artificial cerebrospinal fluid (aCSF), the Morris Water Maze test was used with adult animals to examine their spatial memory and behaviour under stressful conditions. Afterwards the animal brains were collected, and the expression changes of the particular markers in different brain regions were examined. Results showed an increase in GFAP expression in the STZ group, compared to the control group. Both SAL-aCSF and muscimol doses show a decrease in GFAP expression, compared to the STZ group. Iba-1 marker expression showed a tendency to decrease in the M0.05-STZ group, both in the cortex and the hippocampus, and TH marker expression changes were observed only in the cortex, in the M0.01-STZ group. Muscimol shows the ability to decrease STZ induced neuroinflammation and further research is needed to determine the mechanism of action
Oxaliplatin related neurotoxicity research in patients with colorectal cancer
No full textÅ ajÄ pÄtÄ«jumÄ tiek analizÄta oksaliplatÄ«na, kas tiek izmantots kolorektÄlÄ vÄža (KRV) kombinÄtÄ terapijÄ, inducÄta neirotoksicitÄte KRV pacientiem. Bakalaura darba teorÄtiskajÄ daÄ¼Ä tiek apskatÄ«ts oksaliplatÄ«na darbÄ«bas mehÄnisms un tÄ izraisÄ«tÄs blaknes kopumÄ, sÄ«kÄk analizÄta neirotoksicitÄte un iespÄjas to novÄrst, kÄ arÄ« apskatÄ«tas oksaliplatÄ«na Ä·Ä«mijterapijas shÄmas. Darba mÄrÄ·is ir pÄtÄ«t oksaliplatÄ«na neirotoksicitÄtes atkarÄ«bu no kopÄjÄ uzÅemtÄ oksaliplatÄ«na daudzuma, terapijas shÄmas un saistÄ«bu ar pacientu dzÄ«vesveidu. PraktiskajÄ daÄ¼Ä tiek analizÄta uzÅemtÄs devas, Ä·imijterapijas shÄmas un pacientu dzÄ«vesveida ietekme uz oksaliplatÄ«na inducÄtu neirotoksicitÄti. IzdarÄ«tie secinÄjumi ir balstÄ«ti uz 22 KRV pacientu anketÄÅ”anas rezultÄtiem un viÅu ambulatoro kartiÅu izpÄtes datiem laikÄ no 2014.gada februÄra lÄ«dz 2014.gada maijam. AtslÄgas vÄrdi: kolorektÄlais vÄzis, oksaliplatÄ«ns, FOLFOX, neirotoksicitÄte.This study deals with the analysis of the neurotoxicity induced by oxilaplatin, which is used in colorectal cancer chemotherapy. The theoretical part investigates oxilaplatinās mechanism of action and its side effects in general, the analysis of neurotoxicity in particular and possibilities to prevent it, and the study of the chemotherapy treatment plan. The goal of the BA thesis is to research the oxilaplatin-induced neurotoxicity relation to the total cumulative dose of oxilaplatin, the treatment plan and the lifestyle of the patients. The empirical part provides the analysis of the influence of the total cumulative dose of oxilaplatin, the treatment plan and the lifestyle of the patients on the oxilaplatin-induced neurotoxicity. The conclusions drawn are based on the results obtained from the survey and the data from 22 colorectal cancer patientsā ambulatory records during the period from February to May 2014. Key words: colorectal cancer, oxilaplatin, FOLFOX, neurotoxicity
The alterations of Neuroinflammation expression in streptozotocin induced Alzheimers model in rats with muscimol
No full textAlcheimera slimÄ«ba ir biežÄkÄ neirodeÄ£eneratÄ«vÄ slimÄ«ba mÅ«sdienu sabiedrÄ«bÄ, ar tendenci slimnieku skaitam ar katru gadu pieaugt. SarežģītÄs diagnostikas un neefektÄ«vÄs farmakoloÄ£iskÄs terapijas dÄļ, Å”o slimÄ«bu ir grÅ«ti kontrolÄt. PÄtnieki nodarbojas ar Alcheimera slimÄ«bas pirms-demences diagnostikas metožu un veiksmÄ«gas farmakoloÄ£iskÄs terapijas atklÄÅ”anu. Balstoties uz iepriekÅ” veiktiem pÄtÄ«jumiem par GABAA agonista muscimola (0,01 un 0,05 mg/kg) spÄju samazinÄt neiroiekaisumu, streptozocÄ«na (STZ) izraisÄ«tÄ Alcheimera slimÄ«bas modelÄ« žurkÄm [MareÅ” P., et al. 2014], [Ding Y., et al. 2015], Å”ajÄ pÄtÄ«jumÄ tika apskatÄ«ta un analizÄta neiroiekaisuma biomarÄ·ieru ekspresija post mortem žurku smadzenÄs. Darba mÄrÄ·is bija noteikt muscimola ļoti mazo devu (0,01 un 0,05 mg/kg) efektu uz iekaisuma marÄ·ieriem: astroglijas specifisku (glial fibrillary acid protein, GFAP), mikroglijas specifisku (ionized calcium binding adaptor molecule 1, Iba-1) un dopamÄ«nerÄ£iskÄs sistÄmas specifisku tirozÄ«na hidroksilÄzes (TH) ekspresiju smadzeÅu struktÅ«rÄs garozÄ un hipokampÄ Alcheimera slimÄ«bas modelÄ« žurkÄm, kas radÄ«ts ar toksÄ«nu streptozocÄ«nu. Divas nedÄļas pÄc STZ vai mÄkslÄ«gÄ cerebrospinÄlÄ Å”Ä·idruma (aCSF) i.c.v. ievadÄ«Å”anas, pieauguÅ”iem dzÄ«vniekiem tika veikts Morisa Å«dens labirinta tests (Morris water maze), lai pÄrbaudÄ«tu telpisko atmiÅu un uzvedÄ«bu stresa apstÄkļos. PÄc tam tika ievÄktas dzÄ«vnieku smadzenes un, izmantojot imunohistoÄ·Ä«mijas analÄ«zi, pÄtÄ«tas minÄto marÄ·ieru ekspresijas izmaiÅas dažÄdos smadzeÅu reÄ£ionos. RezultÄti uzrÄdÄ«ja GFAP ekspresijas palielinÄjumu STZ grupÄ salÄ«dzimÄjumÄ ar kontroli. SAL+aCSF un muscimola abÄs devÄs redzams samazinÄjums GFAP ekspresijÄ salÄ«dzinÄjumÄ ar STZ grupu. Iba-1 marÄ·iera ekspresijai bija tendence samazinÄties M0,05-STZ grupÄ gan garozÄ, gan hipokampÄ, un TH marÄ·iera ekspresijas izmaiÅas tika novÄrotas garozÄ M0,01-STZ grupÄ. Muscimolam piemÄ«t spÄja mazinÄt iekaisumu, ko izraisÄ«jis streptozocÄ«ns un ir nepiecieÅ”ami tÄlÄki pÄtÄ«jumi, lai noskaidrotu darbÄ«bas mehÄnismu.Alzheimerās disease is the most common neurodegenerative disorder in modern society, and the number of patients tends to increase every year. It is difficult to control the disease because of complicated diagnostics and ineffective pharmacological therapy. Scientists are working on finding diagnostic techniques for Alzheimerās disease at pre-dementia stage and effective pharmacological therapy. Based on the previous studies about the low doses of GABAA agonist muscimolās ability (0.01 and 0.05 mg/kg) to reduce neuroinflammation in a streptozocin (STZ) induced rat model of Alzheimerās disease [Mares P., et al. 2014], [Ding Y., et al. 2015], the expression of the neuroinflammatory biomarkers was investigated and analyzed in post mortem rat brain. The goal of the MA thesis was to determine the effect of muscimol in low doses (0.01 and 0.05 mg/kg) on the particular neuroinflammatory biomarkers: astroglial-specific (glial fibrillary acid protein, GFAP), microglial-specific (ionized calcium binding adaptor molecule 1, Iba-1), and the specific expression of dopaminergic systemās tyrosine hydroxylase (TH) in the cerebral cortex and hippocampus of the streptozocin (STZ) induced rat model of Alzheimerās disease. Two weeks after the i.c.v. injection of STZ or artificial cerebrospinal fluid (aCSF), the Morris Water Maze test was used with adult animals to examine their spatial memory and behaviour under stressful conditions. Afterwards the animal brains were collected, and the expression changes of the particular markers in different brain regions were examined. Results showed an increase in GFAP expression in the STZ group, compared to the control group. Both SAL-aCSF and muscimol doses show a decrease in GFAP expression, compared to the STZ group. Iba-1 marker expression showed a tendency to decrease in the M0.05-STZ group, both in the cortex and the hippocampus, and TH marker expression changes were observed only in the cortex, in the M0.01-STZ group. Muscimol shows the ability to decrease STZ induced neuroinflammation and further research is needed to determine the mechanism of action
Organ-On-A-Chip (OOC) Image Dataset for Machine Learning and Tissue Model Evaluation
No full textOrgan-on-a-chip (OOC) technology has emerged as a groundbreaking approach for emulating the physiological environment, revolutionizing biomedical research, drug development, and personalized medicine. OOC platforms offer more physiologically relevant microenvironments, enabling real-time monitoring of tissue, to develop functional tissue models. Imaging methods are the most common approach for daily monitoring of tissue development. Image-based machine learning serves as a valuable tool for enhancing and monitoring OOC models in real-time. This involves the classification of images generated through microscopy contributing to the refinement of model performance. This paper presents an image dataset, containing cell images generated from OOC setup with different cell types. There are 3072 images generated by an automated brightfield microscopy setup. For some images, parameters such as cell type, seeding density, time after seeding and flow rate are provided. These parameters along with predefined criteria can contribute to the evaluation of image quality and identification of potential artifacts. This dataset can be used as a basis for training machine learning classifiers for automated data analysis generated from an OOC setup providing more reliable tissue models, automated decision-making processes within the OOC framework and efficient research in the future
