mRNA redistribution during permanent focal cerebral ischemia.

Translation arrest occurs in neurons following focal cerebral ischemia and is irreversible in penumbral neurons destined to die. Following global cerebral ischemia, mRNA is sequestered away from 40S ribosomal subunits as mRNA granules, precluding translation. Here, we investigated mRNA granule formation using fluorescence in situ histochemistry out to 8 h permanent focal cerebral ischemia using middle cerebral artery occlusion in Long Evans rats with and without diabetes.

Insulin like growth factor-1 (IGF-1) decreases ischemia-reperfusion induced apoptosis and necrosis in diabetic rats.

Previous evidence supports the view that insulin, as well as insulin like growth factor-1 (IGF-1) provides neurotropic support for neurons in the central nervous system (CNS) and peripheral nervous system (PNS). In the present study we evaluated the effects of the intravenous infusion of IGF-1 on both necrosis and apoptosis in the CNS of streptozotocin induced diabetic animals before and/or following middle cerebral artery occlusion (MCAO) with reperfusion. The lesion volume was used as an index of necrosis and the sensorimotor cortex (layers 5 and 6) as well as the CA1 and CA3 regions of the hippocampus were analyzed for apoptosis using TUNEL staining and Caspase-3 immunoreactivity.

Cerebral ischemia-induced apoptosis and necrosis in normal and diabetic rats: effects of insulin and C-peptide.

Neuronal apoptosis has been demonstrated to be a significant factor in neurological deficiencies associated with diabetes, and these deficiencies are exaggerated following ischemia. Diabetic rats have an increased basal level of apoptosis compared to non-diabetics and it has been previously demonstrated that infarct volumes were greater in diabetic animals following middle cerebral artery occlusion (MCAO) when compared to non-diabetics. In this study, we evaluated both the acute and chronic effects of insulin and/or C-peptide on CNS necrosis and apoptosis in non-diabetic and streptozotocin-induced diabetic rats following MCAO with reperfusion.

The effect of high fat-induced obesity on cardiovascular and physical activity and opioid responsiveness in conscious rats.

Both obesity and increased endorphin production are associated with an increase in blood pressure. We have previously demonstrated that the acute and chronic central nervous system (CNS) administration of beta-endorphin can increase or decrease blood pressure, respectively. Also high fat (HF) diet-induced obesity is associated with increased hypothalamic mu opioid receptors and increased blood pressure in response to ss-endorphins.

The cardiovascular responses to mu opioid agonist and antagonist in conscious normal and obese rats.

Beta-endorphin decreases blood pressure in normal rats but increases blood pressure in obese rats. Since beta-endorphins can bind both mu opioid and kappa-opioid receptors we investigated the effect of a mu specific receptor agonist, D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and a mu specific antagonist, D-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) on cardiovascular responses in conscious control and obese rats. Rats were also implanted with telemetry transmitters and intracerebroventricular (ICV) cannulas for recording and peptide administration.

Cerebral ischemia induced apoptosis and necrosis in normal and diabetic rats.

Stroke is the third leading cause of death and disability, and the risk for ischemic stroke is greater in diabetics. Previous studies have demonstrated both structural and functional nervous system changes in diabetes, and these changes may be enhanced by apoptosis. In the present study, we evaluated several indexes of both necrosis and apoptosis in the CNS of normals and two different models of diabetes (insulinopenic and insulin-resistant).

The effect of global brain ischemia in normal and diabetic animals: the influence of calcium channel blockers.

Diabetes with hypertension is characterized by increased cerebrovascular pathology and poorer outcomes following stroke. In this study we evaluated the effect of global brain ischemia on brain metabolic parameters in normal and diabetic rats treated with a dihydropyridine calcium antagonist, felodipine. Normal and diabetic rats were treated daily with felodipine (5 mg/kg) or saline.

A role for the central histaminergic system in the leptin-mediated increase in cardiovascular dynamics.

The central nervous system (CNS) histaminergic neurons have been shown to regulate feeding behavior and are a target of leptin in the brain. The present study aimed to examine the involvement of the histaminergic system in the leptin-mediated regulation of cardiovascular dynamics. We investigated the cardiovascular responses to the CNS administration of histamine, leptin and alpha-melanocyte stimulating hormone (alpha-MSH) both in the presence and absence of the histamine H1 antagonist, chlorpheniramine.

Diabetes enhances apoptosis induced by cerebral ischemia.

The aim of this study is to explore the mechanism by which diabetes exaggerates cerebral stroke and its outcome. Since ischemia can be related to not only necrosis but apoptosis as well, we compared the development of apoptosis in STZ-diabetic rats and STZ-diabetic rats subjected to occlusion of the middle cerebral artery (MCA). 24-48 hr following MCA occlusion the animals were killed, the brain removed and prepared for evaluation by several indexes of apoptosis: nucleosomal DNA fragmentation, TUNEL staining, activation of caspase-3 and alteration in the expression of Bax and Bcl2.

Effects of C-peptide on expression of eNOS and iNOS in human cavernosal smooth muscle cells.

Objectives: To investigate the role of C-peptide alone or in conjunction with insulin on the expression of nitric oxide synthase (NOS) in human corpus cavernosum smooth muscle cells (HCSMCs). Erectile dysfunction, among diabetic patients, is a significant health problem. The specific causes of erectile dysfunction are unknown.

The effect of CNS opioid on autonomic nervous and cardiovascular responses in diet-induced obese rats.

The intracerebroventricular (i.c.v.

Insulin-mediated increase in sympathetic nerve activity is attenuated by C-peptide in diabetic rats.

Connecting peptide (C-peptide) is secreted along with insulin in equimolar amounts into portal circulation in response to beta cell stimulation. The biological function of C-peptide had been mostly limited to establishing the secondary and tertiary structure of proinsulin. Recent studies have suggested that C-peptide can impact several functions, such as autonomic and sensory nerve function, insulin secretion, and microvascular blood flow.

Expression of cAMP-responsive element modulator (CREM) in rat testes following chronic cocaine administration.

Objective: c-AMP-responsive element modulator (CREM), one of the nuclear factors involved in the regulation of gene expression by cAMP, has an important role in spermatogenesis. Our recent study has shown that chronic administration of cocaine to male rats results in disruption of spermatogenesis, including reduction of germ cells. As a further step toward understanding this process, we have studied the role of CREM in cocaine-induced testicular damage.

High fat feeding is associated with increased blood pressure, sympathetic nerve activity and hypothalamic mu opioid receptors.

Obesity and high fat diets are associated with an increased prevalence of diabetes, cardiovascular disease, and hypertension. However, the mechanism(s) linking obesity and high fat diet to these metabolic and cardiovascular disorders are not fully elucidated. Leptin stimulates the formation of pro-opiomelanocortin and its products.

Cardiovascular responses to central administration of mu and kappa opioid receptor agonist and antagonist in normal rats.

The response to centrally administered beta-endorphin has been characterized by decreasing sympathetic nervous activity and decreased cardiovascular tone. We investigated the effect of the central administration of both mu and kappa opioid receptor agonist and antagonists on cardiovascular responses. The administration of the mu agonist, DAMGO (0.

The effects of middle cerebral artery occlusion on central nervous system apoptotic events in normal and diabetic rats.

Apoptosis and neural degeneration are characteristics of cerebral ischemia and brain damage. Diabetes is associated with worsening of brain damage following ischemic events. In this study, the authors characterize the influence of focal cerebral ischemia, induced by middle cerebral artery occlusion, on 2 indexes of apoptosis, TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end-labeling) staining and caspase-3 immunohistochemistry.

Role of mitochondrial cytochrome c in cocaine-induced apoptosis in rat testes.

Objectives: We have previously demonstrated that cocaine exposure leads to apoptosis in rat testes. To understand further the mechanism of cocaine-induced testicular damage, we studied the effect of cocaine on cytochrome c release from the mitochondria. We also determined the caspase 3, caspase 8, and caspase 9 activities in rat testes after chronic cocaine exposure.

Insulin mediated hemodynamic responses in spontaneous hypertensive rats (SHRs): effect of chromosome 4 gene transfer.

The spontaneous hypertensive rat (SHR) is a widely studied model of essential hypertension and has been reported to exhibit alterations in carbohydrate and lipid metabolism. Genetic linkage studies implicated that SHR carries deletion variant of Cd36 gene of chromosome 4, the gene that encodes fatty acid transporter. Thus it could be possible that primary genetic defect in SHR is compromised tissue utilization of fatty acid that would form the basis for the pathogenesis of hyperinsulinemia, insulin resistance and insulin-mediated responses.

Cardiovascular action of insulin-like growth factor-1 is not mediated by calcitonin gene-related peptide neurons.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator located in the peripheral nerves including the perivascular nerves. Previous studies in our laboratory determined that the vasodilatory action of insulin is mediated in part by CGRP-containing neurons. Since insulin-like growth factor-1 (IGF-1) and insulin share molecular and receptor structural similarity as well as functional similarity, we investigated the role of the CGRP-containing neurons in IGF-1-mediated vasodilation.

Cigarette smoking induces apoptosis in rat testis.

In a previous studywe demonstrated the deleterious effect of cigarette smoke on spermatogenesis in the testis of peripubertal Sprague-Dawley rats. In this study we investigated the development of apoptosis as a possible contributing factor to the pathogenic mechanism underlying these effects. Peripubertal rats were exposed to cigarette smoke with the Walton Horizontal Smoking Machine.

The effects of beta-endorphin (beta-END) on cardiovascular and behavioral dynamics in conscious rats.

Beta-endorphin (beta-END) a product of the proopiomelanocortin (POMC) has been demonstrated to play a role in the regulation of metabolic and autonomic responses. Recent studies have suggested the involvement of the endogenous opioid system in cardiovascular control. Previous studies conducted in our laboratory using anesthetized animals investigated the actions of beta-END and other POMC derived peptides on sympathetic and cardiovascular dynamics.

Chronic nitric oxide deficiency is associated with altered leutinizing hormone and follicle-stimulating hormone release in ovariectomized rats.

Nitric oxide (NO) synthase (NOS) has been found in the gonadotrophs and folliculo-stellate cells of the anterior pituitary. Previous observations from our laboratory suggest that NO may play a role in regulating gonadotropin secretion. Because estrogen secretion by the ovary can influence gonadotropin secretion, we investigated the hypothesis that chronic in vivo NO deficiency has a direct estrogen-independent effect on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion.

The effects of acute and chronic alpha melanocyte stimulating hormone (alphaMSH) on cardiovascular dynamics in conscious rats.

Alpha melanocyte stimulating hormone (alphaMSH) has been demonstrated to have regulatory functions in the periphery and central nervous system (CNS). alphaMSH plays a central role in the regulation of metabolic balance such as decreasing food intake, increasing sympathetic outflow and hypothalamic/pituitary function. Our laboratory has investigated the actions of alphaMSH on sympathetic and cardiovascular dynamics using anesthetized animals.

The insulin-mediated vascular and blood pressure responses are suppressed in CGRP-deficient normal and diabetic rats.

Background: Calcitonin gene-related peptide (CGRP) is extensively localized in the perivascular or periadventitia nerves throughout the body. CGRP is a potent vasodilator and its release is associated with dilation of these blood vessels. The present study investigated the contribution of the CGRP-mediated vasodilation to the insulin-induced vasodilatory response.

Effect of aldose reductase inhibition on interleukin-1beta-induced nitric oxide (NO) synthesis in vascular tissue.

Glucose metabolism via sorbitol pathway has been implicated as a possible contributor to the diabetes-related vascular changes. Nitric oxide plays a major regulatory role in the vascular dilatatory and constricted response. Also it has been observed that diabetes causes vascular changes leading to a decrease in nitric oxide production.