Membrane function alterations in erythrocytes from mood disorder patients

Objectives: To examine erythrocyte membrane functions in mood disorder patients and to establish possible diagnostic marker parameter(s).Design: Collection of blood samples from mood disorder patients and age-matched control volunteers.Preparation of erythrocyte membranes for the proposed studies.Setting: Out patients / in patients, psychiatry ward, Civil Hospital, Ahmedabad, Gujarat, India, Department of Biochemistry, Faculty of Science, M.S.University of Baroda, Vadodara, Gujarat, India.Subjects: Unipolar and bipolar subjects. Control subjects (randomly selected volunteers).Results: The most significant results were a duration dependent decrease in the TPL/CHL ratio (mole:mole),changes in both the substrate and temperature kinetics properties of AChE and elevated plasma BChE activity in the mood disorder patients.Conclusion: The results suggest that the altered lipid profiles and the TPL/CHL (mole: mole) ratio and the altered temperature-dependent activity coefficients of erythrocyte membrane AChE and elevated plasma BChE activities could serve as useful diagnostic pointers for mood disorders.Keywords:Membrane function; Erythrocytes; Mood disorderSA Psych Rev 2003;6:11-2

Cerebral ischemic damage in diabetes: an inflammatory perspective

Stroke is one of the leading causes of death worldwide. A strong inflammatory response characterized by activation and release of cytokines, chemokines, adhesion molecules, and proteolytic enzymes contributes to brain damage following stroke. Stroke outcomes are worse among diabetics, resulting in increased mortality and disabilities. Diabetes involves chronic inflammation manifested by reactive oxygen species generation, expression of proinflammatory cytokines, and activation/expression of other inflammatory mediators. It appears that increased proinflammatory processes due to diabetes are further accelerated after cerebral ischemia, leading to increased ischemic damage. Hypoglycemia is an intrinsic side effect owing to glucose-lowering therapy in diabetics, and is known to induce proinflammatory changes as well as exacerbate cerebral damage in experimental stroke. Here, we present a review of available literature on the contribution of neuroinflammation to increased cerebral ischemic damage in diabetics. We also describe the role of hypoglycemia in neuroinflammation and cerebral ischemic damage in diabetics. Understanding the role of neuroinflammatory mechanisms in worsening stroke outcome in diabetics may help limit ischemic brain injury and improve clinical outcomes

Effect of long-term aluminum feeding on lipid/phospholipid profiles of rat brain myelin

Effect of long-term (90–100 days) exposure of rats to soluble salt of aluminum (AlCl(3)) on myelin lipid profile was examined. The long-term exposure to AlCl(3 )resulted in a 60 % decrease in the total phospholipid (TPL) content while the cholesterol (CHL) content increased by 55 %. Consequently the TPL / CHL molar ratio decreased significantly by 62 %. The phospholipid composition of the myelin membrane changed drastically; the proportion of practically all the phospholipid classes decreased by 32 to 60 % except for phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Of the latter two, proportion of PC was unchanged while PE increased in proportion by 47 %. Quantitatively, all phospholipid classes decreased by from 42 to 76% with no change in the PE content. However the membrane fluidity was not altered in Al-treated rats. Many of the changes we observe here show striking similarities with the reported phospholipid profiles of Alzheimer brains

New mechanistic insights, novel treatment paradigms, and clinical progress in cerebrovascular diseases

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress

Models of cerebral amyloid angiopathy-related intracerebral hemorrhage

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease with vascular amyloid-β deposits and is commonly observed among the elderly. Often associated with Alzheimer’s disease, CAA is among the leading causes of intracerebral hemorrhage (ICH) and age-related cognitive decline. Several research studies have tried to understand the mechanisms underlying CAA, but further use of in vivo models is needed to fully understand its pathophysiology. In this review, we provide information gathered from key findings dealing with the mechanisms of beta deposition in cerebral arteries, the diagnosis of different CAA types, and advances in treatment for CAA. Since CAA is a risk factor for ICH, we also review previously used in vivo and in vitro models of CAA and their features with respect to CAA-related ICH. Currently available transgenic mouse models of CAA show a limited occurrence of hemorrhage at variable locations, which often do not produce any obvious neurological deficits. Thus, the development of novel models to more closely mimic the clinical condition of CAA-related ICH is warranted

Ameliorative potential of conditioning on ischemia-reperfusion injury in diabetes

Diabetes is a serious metabolic disease characterized by hyperglycemia. Diabetes also leads to several long-term secondary complications. Cardiovascular disease is an important complication of diabetes and is a major contributor to morbidity and mortality in diabetic subjects. The discovery of conditioning-induced ischemic or anoxic tolerance has led to the demonstration of the protective potential of conditioning as a treatment strategy to mitigate ischemia-reperfusion injury. Diabetes modulates multiple metabolic pathways and signal transduction cascades. Some of these pathways may overlap with mechanisms that mediate the beneficial effects of conditioning from the body's reaction to a sublethal insult, indicating the possibility of a potential interaction between diabetes and conditioning. Studies demonstrate that diabetes abrogates the ameliorative effect of various forms of conditioning, such as ischemic preconditioning, ischemic postconditioning, remote ischemic conditioning and pharmacological conditioning, on ischemia-reperfusion injury in various animal models. Moreover, drugs used to treat diabetes may have a potential impact on protection afforded by conditioning from ischemic injury. Studies also indicate a potential impact of various anti-diabetic drugs on conditioning-induced protection. Overall, the literature suggests that a better understanding of the overlap among pathways activated by diabetes and those involved in induction of ischemia tolerance may help identify ideal conditioning paradigms to protect diabetic subjects from ischemic injury

Diabetic Rodent Models for Chronic Stroke Studies

Chronic diabetes may cause secondary complications like stroke and also increase post-stroke brain damage. In stroke research, the Stroke Therapy Academic Industry Roundtable (STAIR) identified criteria to increase translational value of preclinical studies, which highlighted the importance of using animal models of comorbidities. Numerous animal models have been used to study the aggravation of ischemic brain damage in diabetics. In this chapter, we discuss rat and mouse models of streptozotocin (STZ)-induced diabetes, with an efficient method provided. We also provide an overview of spontaneously diabetic rodent models. We present different pathophysiological features of diabetes in each rodent model along with the advantages and disadvantages of each model. Utilizing these models may aid the advancement of novel treatments and therapies to lower ischemic brain damage in patients of diabetes

Impact of Hypoglycemia on Brain Metabolism During Diabetes

Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy, because it induces metabolic alterations in the brain. Metabolic alterations are one of the central mechanisms mediating hypoglycemia-related functional changes in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple metabolic pathways, and exposure to hypoglycemia increases consumption of alternate respiratory substrates such as ketone bodies, glycogen, and monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia-induced metabolic alterations in the brain in glucose counterregulation, uptake, utilization and metabolism, cellular respiration, amino acid and lipid metabolism, and the significance of other sources of energy. The present review summarizes information on hypoglycemia-induced metabolic changes in the brain of diabetic and non-diabetic subjects and the manner in which they may affect brain function

Pharmacokinetics of Human Red Blood Cell Microparticles Prepared Using High-Pressure Extrusion Method

Red blood cell microparticles (RMPs) is a high potency hemostatic agent, which may serve as a viable therapeutic approach. They generate thrombin in vitro and effective in arresting bleeding in animal bleeding models. However, prior to ascertaining the clinical efficacy of RMPs, detailed preclinical evaluation is necessary. Therefore, we aimed to characterize RMPs, ascertain their stability, and determine their pharmacokinetics in rats. RMPs were prepared from human RBCs by a high-pressure extrusion method. Pharmacokinetic parameters were computed from groups receiving various RMPs dosing regimens. Volume of distribution, elimination rate constant, and clearance for RMPs were also assessed. Major portion of prepared microparticles were RMPs and a very small portion of particles were from platelets and leukocytes. RMPs were stable when stored at 5 and -20°C for at least 12 months. In vivo half-life was found to vary for each paradigm, but in general, was less than 2 min for most of the paradigms evaluated. Our results demonstrate that RMPs are stable during prolonged storage and have a short half-life. Therefore, the clinical use of RMPs as a hemostatic agent, within a tailored treatment paradigm, may be advantageous in achieving prolonged systemic therapeutic benefit without provoking any thrombotic complications