tretinoin has been researched along with Stroke* in 18 studies
1 review(s) available for tretinoin and Stroke
1 trial(s) available for tretinoin and Stroke
17 other study(ies) available for tretinoin and Stroke
| Article | Year |
|---|---|
Retinoic Acid-Loaded Nanoparticles Promote Neurovascular Protection in Stroke.
Topics: Humans; Nanoparticles; Stroke; Tretinoin | 2023 |
The cardiovascular safety of oral alitretinoin: a population-based cohort study involving 19 513 patients exposed to oral alitretinoin.
Oral alitretinoin is a retinoid used for severe chronic hand eczema. Although caution is recommended for patients with uncontrolled dyslipidaemia or cardiovascular risk factors, the actual atherothrombotic risk has not been investigated thus far.. To detect any excess of atherothrombotic events among patients exposed to alitretinoin, during treatment or in the 2 years following initiation.. Using the French Health Insurance database, we compared the number of patients who had an atherothrombotic event (coronary artery disease, ischaemic stroke or peripheral artery disease requiring revascularization) in the population exposed to oral alitretinoin vs. the general population of the same age, sex and baseline cardiovascular risk, using standardized morbidity ratios (SMRs).. Between 2009 and 2017, 19 513 patients were exposed to oral alitretinoin in France. Sixty-four (0·3%) patients had an atherothrombotic event while on alitretinoin. Patients receiving alitretinoin experienced no more atherothrombotic events than the general population: patients without cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·65 [95% confidence interval (CI) 0·26-1·34] during alitretinoin treatment, and 1·21 (95% CI 0·90-1·59) in the 2 years following initiation; patients with cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·82 (95% CI 0·60-1·08) during alitretinoin treatment and 0·95 (95% CI 0·82-1·09) in the 2 years following initiation. Taken separately, SMRs for each outcome did not increase either.. These data from an exhaustive nationwide population-based study do not support an increase in the incidence of atherothrombotic events with alitretinoin use, regardless of the baseline cardiovascular risk of the patient. Topics: Alitretinoin; Brain Ischemia; Cohort Studies; Dermatologic Agents; Humans; Stroke; Tretinoin | 2021 |
All trans-retinoic acid protects against acute ischemic stroke by modulating neutrophil functions through STAT1 signaling.
Regulation of neural inflammation is considered as a vital therapeutic target in ischemic stroke. All-trans retinoic acid (atRA), a potent immune modulator, has raised interest in the field of stroke therapy. However, the immunological mechanisms for atRA-mediated neuroprotection remain elusive. The current study evaluated the impact of atRA on post-stroke neural inflammation and elucidated the mechanisms involved in the regulation of related neutrophil functions.. atRA was prophylactically administered to mice 1 day before transient middle cerebral artery occlusion (tMCAO, 1 h) and repeated daily immediately after reperfusion for 3 days. Stroke outcomes, neutrophil polarization, and formation of neutrophil extracellular traps (NETs) in the stroke lesion were assessed. Neutrophil depletion was induced with anti-Ly6G antibodies. Primary neutrophil cultures were used to explore the mechanisms of atRA treatment.. Prophylactic atRA treatment reduced infarct volumes and neurological deficits at 1 day after tMCAO. Post-stroke neural inflammation was attenuated and neutrophil accumulation in lesion was downregulated. atRA treatment skewed neutrophil toward N2 phenotype which facilitated its clearance by macrophage and inhibited NETs formation. The functions of neutrophil were indispensable in the protective effects of atRA and were associated with suppression to STAT1 signaling by atRA. Administration of atRA after stroke still provided efficient protection to cerebral ischemia.. atRA displays potent therapeutic efficacy in ischemic stroke by attenuating neural inflammation. Treatment of atRA impeded neutrophil accumulation, favored N2 polarization, and forbade NETs formation in ischemic lesion. STAT1 signaling played a decisive role in the mechanisms of atRA-afforded regulation to neutrophil. Topics: Animals; Brain Ischemia; Cells, Cultured; Female; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Neutrophils; Signal Transduction; STAT1 Transcription Factor; Stroke; Tretinoin | 2019 |
Serum Retinoic Acid Level and The Risk of Poststroke Cognitive Impairment in Ischemic Stroke Patients.
Retinoic acid (RA), an active metabolite of vitamin A, possesses enormous protective effects on vascular systems. It may also be positively related to good functional outcome after ischemic stroke. However, whether circulating RA concentration is associated with poststroke cognitive impairment (PSCI) remains unclear. This study aimed to detect the association between RA level and PSCI among patients with first-ever acute ischemic stroke.. Two hundred and 61 consecutive patients were prospectively recruited during March 2018 and March 2019. Serum RA concentration was measured at admission for all patients. We also performed cognitive function examination using the Montreal Cognitive Assessment (MoCA) at admission and at every follow-up visit. Patients with MoCA score less than 26 were identified as developing PSCI.. The median serum RA level was 2.0 ng/mL (interquartile range, 1.1-3.2 ng/mL) after admission. Patients diagnosed as PSCI at admission, 1-month and 3-month were 53 (20.3%), 91 (34.6%), and 141 (54.0%), respectively. Univariate analysis showed that reduced RA level was correlated with PSCI at 3-month (P = .003), but not at admission (P = .416) and 1-month poststroke (P = .117). After adjusting for all potential confounders, the odds ratio for the lowest tertile of RA, compared with the highest tertile, was 1.97 (95% confidence interval, 1.01-3.83, P = .046) for PSCI at 3 months. Furthermore, multiple-adjusted spline regression model further confirmed the dose-response relationships between RA level and 3-month PSCI (P < .001).. Decreasing serum RA level might be associated with 3-month PSCI in ischemic stroke patients. Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Cognition; Cognitive Dysfunction; Female; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Tretinoin | 2019 |
Association between serum retinoic acid levels and risk of post-stroke depression in patients with ischemic stroke.
Previous studies suggest that retinoic acid (RA) can exert neuroprotective function in ischemic stroke. However, its role in post-stroke depression (PSD) has still been unclear. We sought to investigate the relationship between circulating RA levels and PSD in patients with ischemic stroke. From September 2018 to March 2019, we prospectively screened patients with ischemic stroke who were hospitalized within 7 days of symptoms onset. RA levels were measured after admission. All patients were followed up at 3 months after stroke. Diagnosis of PSD was made in line with the Chinese version of Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. PSD risk was estimated using multivariable regression models. In total, 352 ischemic stroke patients were enrolled for the final analysis. Up to 3 months after symptoms onset, 102 subjects experienced PSD. PSD patients showed significantly lower RA levels at baseline as compared to non-PSD patients. In univariate logistic analysis, reduced levels of RA was a significant predictor of PSD. These results were further confirmed in multivariate regression additionally controlled for possible relevant confounders. Our study shows that decreased serum RA levels at admission might be associated with 3-month PSD in ischemic stroke patients. Topics: Aged; Brain Ischemia; Depression; Female; Humans; Male; Middle Aged; Prospective Studies; Stroke; Tretinoin | 2019 |
Lower serum retinoic acid level for prediction of higher risk of mortality in ischemic stroke.
To explore the association between serum retinoic acid (RA) level in patients with acute ischemic stroke (AIS) and mortality risk in the 6 months after admission.. From January 2015 through December 2016, patients admitted to 3 stroke centers in China for first-ever AIS were screened. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality in the 6 months after admission. The significance of serum RA level, NIH Stroke Scale score, and established risk factors in predicting mortality were determined. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in statistical analysis.. Of the 1,530 patients enrolled, 325 died within 6 months of admission, with an all-cause mortality of 21.2% and CVD-related mortality of 13.1%. In multivariable analysis, RA levels were expressed as quartiles with the clinical variables. The results of the second to fourth quartiles (Q2-Q4) were compared with the first quartile (Q1); RA levels showed prognostic significance, with decreased all-cause and CVD mortality of 55% and 63%, respectively. After RA was added to the existing risk factors, all-cause mortality could be better reclassified, in association with only the NRI statistic (. Low circulating levels of RA were associated with increased risk of all-cause and CVD mortality in a cohort of patients with first-incidence AIS, indicating that RA level could be a predictor independent of established conventional risk factors. Topics: Aged; Aged, 80 and over; Brain Ischemia; Cause of Death; Cerebrovascular Disorders; China; Cohort Studies; Female; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Predictive Value of Tests; Risk Factors; Stroke; Survival Analysis; Treatment Outcome; Tretinoin | 2019 |
Retinoic acid-pretreated Wharton's jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury.
Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines. Topics: Animals; Brain-Derived Neurotrophic Factor; Cytokines; Disease Models, Animal; Infarction, Middle Cerebral Artery; Lateral Ventricles; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nestin; Rats; Rats, Wistar; Retinoid X Receptor beta; SOXB1 Transcription Factors; Stroke; Tretinoin; Triiodothyronine; Wharton Jelly | 2017 |
Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia.
Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature. Topics: Animals; Cell Death; Cell Differentiation; Cell Proliferation; Cell Survival; Drug Carriers; Humans; Ischemia; Mice; Nanoparticles; Neovascularization, Physiologic; Neural Stem Cells; Neurogenesis; Polymers; Stroke; Tretinoin | 2016 |
Col1a1+ perivascular cells in the brain are a source of retinoic acid following stroke.
Perivascular stromal cells (PSCs) are a recently identified cell type that comprises a small percentage of the platelet derived growth factor receptor-β+ cells within the CNS perivascular space. PSCs are activated following injury to the brain or spinal cord, expand in number and contribute to fibrotic scar formation within the injury site. Beyond fibrosis, their high density in the lesion core makes them a potential significant source of signals that act on neural cells adjacent to the lesion site.. Our developmental analysis of PSCs, defined by expression of Collagen1a1 in the maturing brain, revealed that PSCs first appear postnatally and may originate from the meninges. PSCs express many of the same markers as meningeal fibroblasts, including expression of the retinoic acid (RA) synthesis proteins Raldh1 and Raldh2. Using a focal brain ischemia injury model to induce PSC activation and expansion, we show a substantial increase in Raldh1+/Raldh2+ PSCs and Raldh1+ activated macrophages in the lesion core. We find that RA levels are significantly elevated in the ischemic hemisphere and induce signaling in astrocytes and neurons in the peri-infarct region.. This study highlights a dual role for activated, non-neural cells where PSCs deposit fibrotic ECM proteins and, along with macrophages, act as a potentially important source of RA, a potent signaling molecule that could influence recovery events in a neuroprotective fashion following brain injury. Topics: Animals; Animals, Newborn; Brain; Collagen Type I; Collagen Type I, alpha 1 Chain; Disease Models, Animal; Immunohistochemistry; Infarction, Middle Cerebral Artery; Male; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Transgenic; Pericytes; Stroke; Stromal Cells; Tretinoin | 2016 |
Retinoic acid ameliorates blood-brain barrier disruption following ischemic stroke in rats.
The intact blood-brain barrier (BBB) is essential in maintaining a stabilized milieu for synaptic and neuronal functions. Disruptions of the BBB have been observed following ischemia and reperfusion, both in patients and in animal models. Retinoic acid (RA), which plays crucial roles during vertebrate organogenesis, has been reported to participate in BBB development. However, it remains unclear whether RA could prevent BBB disruption in ischemic stroke. In this study, we determined that the injection of RA for 4 consecutive days resulted in increases in zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) expression, which are crucial components of the BBB structure. We demonstrated that RA pretreatment could alleviate the ischemic stroke-induced enlargement of vascular permeability, which is related to the up-regulated expression of ZO-1 and VE-cadherin proteins in rat models of middle cerebral artery occlusion (MCAO). Our findings further corroborated that the RA protective effect on BBB is dependent on RA receptor α in vitro oxygen-glucose deprivation (OGD) treatment. Significantly, RA administration immediately after MCAO reduced tissue plasminogen activator (tPA)-induced intracerebral hemorrhage (ICH) and ameliorated neurological deficits 24h after ischemic stroke. Taken together, our results suggest that RA may become a new therapeutic approach to prevent BBB dysfunction and tPA-induced ICH in ischemic stroke. Topics: Animals; Antigens, CD; Blood-Brain Barrier; Cadherins; Capillary Permeability; Cell Line; Disease Models, Animal; Injections, Intraperitoneal; Male; Rats; Rats, Sprague-Dawley; Stroke; Tretinoin; Zonula Occludens-1 Protein | 2015 |
[Effect of all-trans retinoic acid on cerebral ischemia injury and regulatory T cell accounts in stroke mice].
To investigate the cerebral infarct volume 24 hours after transient middle cerebral artery occlusion (tMCAO) and the proportion of CD4⁺;CD25⁺;Foxp3⁺; regulatory T cells (Tregs) in splenocytes in diverse periods after all-trans retinoic acid (ATRA) treatment in mice, so as to explore whether ATRA have the protection against cerebral ischemia damage in mice through intervening Treg differentiation.. Sixty male Kunming mice were randomly divided into two groups, i.e. pretreatment (n=40) and post-treatment (n=20) groups. Each group was against divided into two subgroups, i.e. tMCAO combined with ATRA treatment group, tMCAO combined with DMSO control group. Pretreatment groups: mice were treated intraperitoneally with ATRA (10 mg/kg) dissolved in 100 mL/L DMSO or equivalent volume of 100 mL/L DMSO daily for 7 days (n=20/group). Ten mice in each group were sacrificed and the proportion of Tregs in splenocytes was analyzed by flow cytometry (FCM) after 7-day pretreatment. The other 10 mice in each group were subjected to tMCAO by modified monofilament method. Neurologic deficit score (NDS) was recorded and the infarct volume was assessed by 2, 3, 5-triphenyltetrazolium chloride(TTC) staining 24 hours after tMCAO. The mice in post-treatment groups were treated intraperitoneally with ATRA (10 mg/kg) or equivalent volume of 100 mL/L DMSO immediately after the reperfusion of tMCAO modeling (n=10/group). NDS and infarct volume were assessed and the proportion of Tregs in splenocytes was analyzed 24 hours after tMCAO.. ATRA pretreatment for 7 days failed to improve neurologic function deficit (P>0.05) and to reduce the cerebral infarct volume (P>0.05) 24 hours after tMCAO in mice. ATRA post-treatment could markedly improve neurologic function (P<0.05) and reduce the cerebral infarct volume (P<0.05) 24 hours after tMCAO. However, neither ATRA pretreatment nor post-treatment had effect on the proportion of Tregs in the splenocytes of mice (P>0.05).. ATRA administered before tMCAO for 7 days failed to protect brain against ischemic damage. ATRA administered immediately following tMCAO induced cerebral protective effect 24 hours after tMCAO. The results suggest that Tregs change is not involved in the neuroprotection mechanism of ATRA. Topics: Animals; Brain Ischemia; Cerebral Infarction; Flow Cytometry; Infarction, Middle Cerebral Artery; Male; Mice; Neuroprotective Agents; Random Allocation; Spleen; Stroke; T-Lymphocytes, Regulatory; Time Factors; Tretinoin | 2014 |
Electroacupuncture promotes neurological functional recovery via the retinoic acid signaling pathway in rats following cerebral ischemia-reperfusion injury.
Neurogenesis is regulated by a number of signaling pathways, including the retinoic acid (RA) pathway, a key regulator of neurogenesis in the subventricular zone (SVZ) and hippocampus. Acupuncture has been used to treat neurological conditions and is known to potentially enhance cell proliferation in the neurogenic area (hippocampal dentate gyrus and the SVZ of the lateral ventricle walls) in pathological conditions, which is associated with improved brain function. However, whether or not the neuroprotective effects of electroacupuncture (EA) are mediated by the regulation of the RA signaling pathway remains to be determined. Using a transient middle cerebral artery occlusion model, in the present study we evaluated the effect of EA on the neurological functional recovery, infarction volume and investigated the underlying molecular mechanisms. Two hundred and sixteen SD rats were randomly divided into 3 groups: sham, model group (ischemic rats without EA stimulation) and EA group (ischemic rats with EA stimulation on ST36 and LI11). Behavioral deficits were detected with high-resolution digital analysis of 24-h home-cage video recordings. Infarct volume was determined by triphenyltetrazolium hydrochloride staining and the expression of RA mRNA and protein was measured using RT-PCR and western blotting, respectively. We found that EA decreased the infarct volume, promoted neurological functional recovery and increased the RA mRNA and protein expression, compared with the model group. Findings of this study suggest that promoting neurological functional recovery by modulating RA expression in the post-ischemic brain is one of the mechanisms by which EA can be effective in the treatment of ischemic stroke. Topics: Animals; Brain; Brain Ischemia; Cell Proliferation; Disease Models, Animal; Electroacupuncture; Hippocampus; Infarction, Middle Cerebral Artery; Lateral Ventricles; Male; Neurogenesis; Rats; Rats, Sprague-Dawley; Recovery of Function; Reperfusion Injury; Signal Transduction; Stroke; Tetrazolium Salts; Tretinoin | 2013 |
A case of ischemic stroke in acute promyelocytic leukemia at initial presentation. Relevance of all-trans retinoic acid treatment.
Acute promyelocytic leukemia (APL) is frequently associated, often from the earliest phases, with a life-threatening coagulation/bleeding syndrome; disseminated intravascular coagulation (DIC) is described in majority of patients. We report a case of 49-year-old male, without cardiovascular risk factors, who suddenly developed ischemic stroke and splenic infarction as presenting symptoms of APL and related DIC. The patient was immediately treated with all-trans retinoic acid (ATRA) and the alterations of hemocoagulation parameters promptly returned in normal range. The coagulation/bleeding syndrome of the onset of APL is associated with high mortality; both diagnostic and therapeutic approaches require special and timely consideration of this condition. Treatment with ATRA is essential. Topics: Antineoplastic Agents; Disseminated Intravascular Coagulation; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Stroke; Tretinoin | 2010 |
Neural stem cells reduce brain injury after unilateral carotid ligation.
Neonatal stroke presents with seizures and results in neurologic morbidity, including epilepsy, hemiparesis, and cognitive deficits. Stem cell-based therapy offers a possible therapeutic strategy for neonatal stroke. We developed an immature mouse model of stroke with acute seizures and ischemic brain injury. Postnatal day 12 CD1 mice received right-sided carotid ligation. Two or 7 days after ligation, mice received an intrastriatal injection of B5 embryonic stem cell-derived neural stem cells. Four weeks after ligation, hemispheric brain atrophy was measured. Pups receiving stem cells 2 days after ligation had less severe hemispheric brain atrophy compared with either noninjected or vehicle-injected ligated controls. Transplanted cells survived, but 3 out of 10 pups injected with stem cells developed local tumors. No difference in hemispheric brain atrophy was seen in mice injected with stem cells 7 days after ligation. Neural stem cells have the potential to ameliorate ischemic injury in the immature brain, although tumor development is a serious concern. Topics: Animals; Atrophy; Brain Ischemia; Brain Neoplasms; Carotid Arteries; Cell Survival; Ligation; Mice; Neurons; Seizures; Stem Cell Transplantation; Stem Cells; Stereotaxic Techniques; Stroke; Teratoma; Tretinoin | 2008 |
Transplantation of post-mitotic human neuroteratocarcinoma-overexpressing Nurr1 cells provides therapeutic benefits in experimental stroke: in vitro evidence of expedited neuronal differentiation and GDNF secretion.
Nurr1 has been implicated as a transcription factor mediating the endogenous neuroprotective mechanism against stroke. We examined the in vivo and in vitro properties of a new human embryonic carcinoma Ntera-2 cell line carrying the human Nurr1 gene (NT2N.Nurr1). Adult Sprague-Dawley rats underwent experimental stroke initially and 14 days later were assigned randomly to receive stereotaxic transplantation of NT2N.Nurr1 cells or infusion of vehicle into their ischemic striatum. Transplantation of NT2N.Nurr1 cells promoted significant attenuation of behavioral impairments over a 56-day period after stroke, characterized by decreased hyperactivity, biased swing activity, and neurologic deficits, as well as significant reduction in ischemic striatal cell loss compared to vehicle-infused stroke animals. Transplanted NT2N.Nurr1 cells survived and expressed neuronal phenotypic markers in the ischemic striatum. In vitro results showed that cultured NT2.Nurr1 cells were already negative for nestin even before retinoic acid treatment, despite strong nestin immunoreactivity in NT2 cells. This indicates Nurr1 triggered a rapid commitment of NT2 cells into a neuronal lineage. Indeed, NT2.Nurr1 cells, at 4 weeks into RA treatment, displayed more abundant tyrosine hydroxylase positive cells than NT2 cells. Parallel ELISA studies showed further that cultured NT2N.Nurr1, but not NT2N cells, secreted glial cell derived neurotrophic factor. The present study shows efficacy of NT2N.Nurr1 cell grafts in ischemic stroke, with in vitro evidence suggesting the cells' excellent neuronal differentiation capability and ability to secrete GDNF as likely mechanisms mediating the observed therapeutic benefits. Topics: Animals; Behavior, Animal; Carcinoma; Cell Differentiation; Cell Line, Tumor; Cell Transplantation; Corpus Striatum; Disease Models, Animal; DNA-Binding Proteins; Enzyme-Linked Immunosorbent Assay; Glial Cell Line-Derived Neurotrophic Factor; Humans; Male; Motor Activity; Multivariate Analysis; Nerve Tissue Proteins; Nuclear Receptor Subfamily 4, Group A, Member 2; Rats; Rats, Sprague-Dawley; Stroke; Time Factors; Transcription Factors; Tretinoin | 2007 |
Transplantation of neural cells derived from retinoic acid-treated cynomolgus monkey embryonic stem cells successfully improved motor function of hemiplegic mice with experimental brain injury.
We induced neural cells by treating cynomolgus monkey embryonic stem (ES) cells with retinoic acid. The treated cells mainly expressed betaIIItubulin. They further differentiated into neurons expressing neurofilament middle chain (NFM) in elongated axons. Half of the cells differentiated into Islet1+ motoneurons in vitro. The monkey ES-derived neural cells were transplanted to hemiplegic mice with experimental brain injury mimicking stroke. The neural cells that had grafted into periventricular area of the mice distributed extensively over the injured cortex. Some of the transplanted cells expressed the neural stem/progenitor marker nestin 2 days after transplantation. The cells expressed markers characteristic of mature motoneurons 28 days after transplantation. Mice with the neural cell graft gradually recovered motor function, whereas control animals remained hemiplegic. This is the first demonstration that neural cells derived from nonhuman primate ES cells have the ability to restore motor function in an animal model of brain injury. Topics: Animals; Biomarkers; Brain Damage, Chronic; Cell Differentiation; Cell Line; Cell Movement; Cerebral Infarction; Disease Models, Animal; Female; Graft Survival; Hemiplegia; Intermediate Filament Proteins; Macaca fascicularis; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Nestin; Neurofilament Proteins; Neurons; Recovery of Function; Stem Cell Transplantation; Stem Cells; Stroke; Treatment Outcome; Tretinoin | 2005 |
Comparison of calcium-binding proteins expressed in cultured hNT neurons and hNT neurons transplanted into the rat striatum.
An alternative source of cells for neural transplantation and brain repair that has many characteristics of immature neurons is the hNT neuron, derived from an embryonal human teratocarcinoma (NTera2) cell line that is terminally differentiated in vitro with retinoic acid. The majority of hNT neurons are GABAergic in cell culture. We have determined the calcium-binding protein (CBP) phenotypes of hNT neurons for three CBPs, calretinin (CR), calbindin D-28K (CB), and parvalbumin (PV), in cell culture and after transplantation into the rat striatum. In cell culture, 95% of all cell profiles were human nuclear matrix antigen (NuMA) positive. PV-positive hNT neurons constituted 50% of all neuron-like profiles, with CB+ and CR+ constituting 14 and 6% of cells, respectively. In contrast, when the striatal grafts were examined after 30 days survival using confocal microscopy, only 10% of hNT neurons immunopositive for NuMA were PV+; 19% were CB+/NuMA+, approximately the same percentage as was seen in vitro, and 82% of grafted hNT neurons were CR+. These results suggest that hNT neurons can be subdivided into at least three subpopulations based on the CBP phenotype that they express and that there is a CBP phenotypic shift following transplantation. Three related hypotheses are proposed to account for this phenotypic shift of hNT neurons after transplantation: (a) selective survival of the CR+ subpopulation of hNT neurons, (b) selective transitory quiescence of the transplanted PV+ cells due to transplantation stress, or (c) dedifferentiation of the hNT neurons following transplantation, which may allow them to respond to local environmental cues during the engraftment process. Topics: Animals; Antigens, Nuclear; Brain Tissue Transplantation; Calcium-Binding Proteins; Cell Cycle Proteins; Cell Differentiation; Cells, Cultured; Corpus Striatum; Cryopreservation; Embryonal Carcinoma Stem Cells; Female; Fetal Tissue Transplantation; Graft Survival; Humans; Neoplastic Stem Cells; Neurons; Nuclear Matrix-Associated Proteins; Nuclear Proteins; Phenotype; Rats; Rats, Sprague-Dawley; Stroke; Teratocarcinoma; Transplantation, Heterologous; Tretinoin; Tyrosine 3-Monooxygenase | 2001 |