Abstract
We have shown previously that heat stroke produced by whole body hyperthermia (WBH) for 4 h at 38°C in diabetic rats exacerbates blood-brain barrier breakdown, brain edema formation and neuronal cell injury as compared to healthy animals after identical heat exposure. In this combination of diabetes and WBH, normal therapeutic measures do not induce sufficient neuroprotection. Thus, we investigated whether nanowired mesenchymal cells (MSCs) when delivered systemically may have better therapeutic effects on brain damage in diabetic rats after WBH. Diabetes induced by streptozotocin administration (75 mg/kg, i.p, daily for 3 days) in rats resulted in clinical symptoms of the disease within 4 to 6 weeks (blood glucose level 20 to 30 mmoles/l as compared to saline control groups (4 to 6 mmoles/l). When subjected to WBH, these diabetic rats showed a 4-to 6-fold exacerbation of blood-brain barrier breakdown to Evans blue and radioiodine, along with brain edema formation and neuronal cell injury. Intravenous administration of rat MSCs (1x106) to diabetic rats one week before WBH slightly reduced brain pathology, whereas TiO2 nanowired MSCs administered in an identical manner resulted in almost complete neuroprotection. On the other hand, MSCs alone significantly reduced brain pathology in saline-treated rats after WBH. These observations indicate that nanowired delivery of stem cells has superior therapeutic potential in heat stroke with diabetes, pointing to novel clinical perspectives in the future.
Keywords: Blood-brain barrier, brain edema, brain pathology, diabetes, mesenchymal stem cells, neuronal injury, neuroprotection, nanowiring, streptozotocin, TiO2 nanowires, whole body hyperthermia.
CNS & Neurological Disorders - Drug Targets
Title:TiO2-Nanowired Delivery of Mesenchymal Stem Cells Thwarts Diabetes- Induced Exacerbation of Brain Pathology in Heat Stroke: An Experimental Study in the Rat Using Morphological and Biochemical Approaches
Volume: 14 Issue: 3
Author(s): Hari S. Sharma, Lianyuan Feng, Jose V. Lafuente, Dafin F. Muresanu, Zhenrong R. Tian, Ranjana Patnaik and Aruna Sharma
Affiliation:
Keywords: Blood-brain barrier, brain edema, brain pathology, diabetes, mesenchymal stem cells, neuronal injury, neuroprotection, nanowiring, streptozotocin, TiO2 nanowires, whole body hyperthermia.
Abstract: We have shown previously that heat stroke produced by whole body hyperthermia (WBH) for 4 h at 38°C in diabetic rats exacerbates blood-brain barrier breakdown, brain edema formation and neuronal cell injury as compared to healthy animals after identical heat exposure. In this combination of diabetes and WBH, normal therapeutic measures do not induce sufficient neuroprotection. Thus, we investigated whether nanowired mesenchymal cells (MSCs) when delivered systemically may have better therapeutic effects on brain damage in diabetic rats after WBH. Diabetes induced by streptozotocin administration (75 mg/kg, i.p, daily for 3 days) in rats resulted in clinical symptoms of the disease within 4 to 6 weeks (blood glucose level 20 to 30 mmoles/l as compared to saline control groups (4 to 6 mmoles/l). When subjected to WBH, these diabetic rats showed a 4-to 6-fold exacerbation of blood-brain barrier breakdown to Evans blue and radioiodine, along with brain edema formation and neuronal cell injury. Intravenous administration of rat MSCs (1x106) to diabetic rats one week before WBH slightly reduced brain pathology, whereas TiO2 nanowired MSCs administered in an identical manner resulted in almost complete neuroprotection. On the other hand, MSCs alone significantly reduced brain pathology in saline-treated rats after WBH. These observations indicate that nanowired delivery of stem cells has superior therapeutic potential in heat stroke with diabetes, pointing to novel clinical perspectives in the future.
Export Options
About this article
Cite this article as:
Sharma S. Hari, Feng Lianyuan, Lafuente V. Jose, Muresanu F. Dafin, Tian R. Zhenrong, Patnaik Ranjana and Sharma Aruna, TiO2-Nanowired Delivery of Mesenchymal Stem Cells Thwarts Diabetes- Induced Exacerbation of Brain Pathology in Heat Stroke: An Experimental Study in the Rat Using Morphological and Biochemical Approaches, CNS & Neurological Disorders - Drug Targets 2015; 14 (3) . https://dx.doi.org/10.2174/1871527314666150318114335
DOI https://dx.doi.org/10.2174/1871527314666150318114335 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases
Current Medicinal Chemistry Circadian Rhythm in Cytokines Administration
Mini-Reviews in Medicinal Chemistry The Effect of Licorice Drink on the Systemic Exposure of Verapamil in Rabbits
Drug Metabolism Letters The Role of a Human Hematopoietic Mesenchymal Progenitor in Wound Healing and Fibrotic Diseases and Implications for Therapy
Current Stem Cell Research & Therapy Cardiac (myo)fibroblast: Novel Strategies for its Targeting Following Myocardial Infarction
Current Pharmaceutical Design Cardiac Stem Cell Regeneration in Metabolic Syndrome
Current Pharmaceutical Design Targeting Resveratrol to Mitochondria for Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Chemistry and Pharmacology of Angiotensin-Converting Enzyme Inhibitors
Current Pharmaceutical Design Mitochondria Damage in the Pathogenesis of Diabetic Retinopathy and in the Metabolic Memory Associated with its Continued Progression
Current Medicinal Chemistry Side Effects of Clozapine and Some Other Psychoactive Drugs
Current Drug Safety MicroRNA-130a Regulation of Desmocollin 2 in a Novel Model of Arrhythmogenic Cardiomyopathy
MicroRNA Emerging Concepts for Myocardial Late Gadolinium Enhancement MRI
Current Cardiology Reviews Prognostic Utility of Troponin I and N Terminal-ProBNP among Patients with Heart Failure due to Non-Ischemic Cardiomyopathy and Important Correlations
Cardiovascular & Hematological Agents in Medicinal Chemistry Anti-Diabetic Effects of Isolated Lipids from Natural Sources through Modulation of Angiogenesis
Current Molecular Pharmacology The Prostaglandin Agonist Beraprost Aggravates Doxorubicin-mediated Apoptosis by Increasing iNOS Expression in Cardiomyocytes
Current Vascular Pharmacology Mitochondrial Uncoupler Proteins
Current Enzyme Inhibition Cross Talk between the Cardiovascular and Nervous Systems:Neurotrophic Effects of Vascular Endothelial Growth Factor (VEGF) and Angiogenic Effects of Nerve Growth Factor (NGF)-Implications in Drug Development
Current Pharmaceutical Design Virus-Associated Vasculitides: An Update
Current Immunology Reviews (Discontinued) Defensive and Offensive Cross-Reactive Antibodies Elicited by Pathogens: The Good, the Bad and the Ugly
Current Medicinal Chemistry Extrahepatic Targets and Cellular Reactivity of Drug Metabolites
Current Medicinal Chemistry