Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state.

In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase 2A (PP2A) activity, and modulating the redox state. Male F344 rats aged 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received subcutaneous injections of vitamin D (1, α25-dihydroxyvitamin D3) for 21 days. Control animals (n=10 young and n=10 aged) received equal volume of normal saline and behavioral testing in the water maze started on day 14 after the initiation of vitamin D supplementation. Tau phosphorylation, markers of brain energy metabolism (ADP/ATP ratio and adenosine monophosphate-activated protein kinase) and redox state (levels of reactive oxygen species, activity of superoxide dismutase, and glutathione levels) as well as PP2A activity were measured in hippocampal tissues. Our results extended previous findings that: (1) tau phosphorylation significantly increased during aging; (2) markers of brain energy metabolism and redox state are significantly decreased in aging; and (3) aged rats demonstrated significant learning and memory impairment. More importantly, we found that age-related changes in brain energy metabolism, redox state, and cognitive function were attenuated by vitamin D supplementation. No significant differences were seen in tau hyperphosphorylation, markers of energy metabolism and redox state in the young animal groups. Our data suggest that vitamin D ameliorated the age-related tau hyperphosphorylation and cognitive decline by enhancing brain energy metabolism, redox state, and PP2A activity making it a potentially useful therapeutic option to alleviate the effects of aging.

Chronic binge-like alcohol consumption in adolescence causes depression-like symptoms possibly mediated by the effects of BDNF on neurogenesis.

Here we investigated whether changes in neurogenesis and brain-derived neurotrophic factor (BDNF) expression are possible mechanisms involved in the depression-like symptom during the withdrawal/abstinence period after chronic binge-pattern alcohol consumption given the limited number of studies addressing the link between these factors in the adolescent brain. Forty-seven male Sprague-Dawley rats were used in the study and the experimental protocol started when rats were 25-days old. Rats were assigned to either: (a) ethanol or (b) control group. Animals in each group were further randomized to receive either: BDNF receptor agonist or vehicle. Rats were trained to self-administer ethanol and the binge protocol consisted of daily 30-min experimental sessions 4h into the dark period for 12days. Two days after the last drinking session, rats were tested in the sucrose preference test to evaluate anhedonia and the open field test after habituation to evaluate behavioral despair. Our data showed that: (1) self-administration of alcohol in a binge-like pattern causes inebriation as defined by the National Institute on Alcohol Abuse and Alcoholism and this pattern of alcohol exposure is associated with the development of a depression-like symptom; (2) no significant difference in blood alcohol levels between the two ethanol groups; and (3) chronic binge drinking resulted in the development of a depressive phenotype, decreased survival and neuronal differentiation of neural progenitor cells in the hippocampus, and decreased BDNF effect during the withdrawal period. But the most important finding in our study is that augmenting BDNF actions through the use of tyrosine kinase B (TrkB, a BDNF receptor) agonist restored neurogenesis and abolished the alcohol-induced anhedonia and despair behaviors seen during the withdrawal/abstinence period. Our results suggest that BDNF might be a molecule that can be targeted for interventions in alcoholism-depression co-incidence.

Behavioral effects of transient cerebral ischemia.

CA1 neurons in the hippocampus, a brain structure involved in learning and memory, are selectively vulnerable to ischemic effects. In this study, the authors examined if duration of ischemia is directly related to extent of CA1 damage and degree of spatial learning deficit. Adult female Wistar rats received either 5-min or 10-min ischemia or sham surgery. Following recovery, rats were tested in the Morris water maze. Histological analysis showed moderate cell loss in CA1 (31%) and CA3 (12%) and minimal cell loss in CA2 (4%) with 5-min ischemia. Increased cell loss was seen in CA1 (68%), CA2 (16%), and CA3 (23%) with 10-min ischemia. Behavioral testing revealed that animals with 10-min ischemia have greater spatial learning deficits and they remain impaired across the test days compared to the 5-min ischemic group. Furthermore, degree of CA1 cell loss accounted for approximately 45% of the variance in spatial learning deficits in the ischemic group. The authors conclude that cell loss is largely confined to CA1 region in rats who received 5 and 10 min of ischemia and that increased ischemic duration results in persistent learning deficits in female rats; also, the degree of behavioral impairment is related to extent of CA1 cell loss.

Effects of environment on enhancing functional plasticity following cerebral ischemia.

Given the brain's capacity to recover from injury, plasticity may be enhanced following cerebral ischemia through environmental manipulation. Thus, the purpose of this study was to (1) determine the effects of early exposure to an enriched environment following ischemia on functional plasticity and (2) examine the relationship between morphological and behavioral plasticity. Adult female rats (n = 38) were divided into ischemia and control groups. Each group was further randomized to either standard (SC) or enriched conditions (EC). After 4 days of environmental exposure, rats were tested for 6 days in the water maze. Control and ischemia rats exposed to EC have increased total dendritic length (P < 0.05) as well as increased number of dendritic segments in the apical (P < 0.05) region of the hippocampal area compared to those housed in SC; furthermore, increased dendritic spine density in the apical (P < 0.05) region was also seen. Behavioral testing showed that ischemia rats exposed to SC have longer swim latencies (P < 0.05) and greater directional heading errors (P < 0.05) than ischemic rats exposed to EC; the latter group performed similar to controls. It is concluded that EC may be a potentially useful therapy in the recovery of spatial memory impairments seen after ischemia.

Pressure controlled inverse ratio ventilation in respiratory failure.

Since the earliest use of mechanical ventilation for respiratory insufficiency the search has been on for optimal ventilation attuned to different degrees of pulmonary involvement. Pressure controlled inverse ratio ventilation is a recently described ventilatory modality, in which the conventional inspiratory to expiratory ratio is reversed. This method of ventilation allows for stabilization of pulmonary units and diffusion of gases.

Families: a link or a liability?

Hospitalization in a critical care setting has multiple effects on patients and their families. For patients, it can be a frightening and dehumanizing experience, while families are confronted with stressors that can disrupt normal family functioning. The nurse is the pivotal figure in the health care system who can positively affect family coping through the support offered. With family needs met, they are then strengthened and able to support their family member. This article examines the roles and relationships of families, social support systems, and nurses. Through the framework of social support, nurses provide emotional, instrumental, spiritual, and appraisal assistances to families. This can potentially positively affect the family's adaptation to a stressful situation, and thus the family's ability to provide support to the patient. A case study analysis is described to illustrate the interactions and interventions through a model of family support.

A family-centered critical care unit.

Although care of the family has long been a focus of nursing, there has been an increased emphasis in recent years to provide opportunities for families to be an integral part of the hospitalization experience. This has been difficult for many nurses who perceive themselves as competent to care for a patient in "medical crisis" but feel unqualified to provide family care. This article will address issues related to implementing a family-centered philosophy of care in a critical care unit. Implementation strategies that will be discussed include: formulating a staff-led family support group and family committee, instituting a family visitation contract within open visitation parameters, and developing clinicians with expertise in family care. Tools such as a performance plan for a Clinical Nurse II specializing in family care and the family visitation contract will be shared.

Tissue-plasminogen activator: nursing implications.

Coronary thrombolysis has been proved to be beneficial in the treatment of myocardial infarction. Much attention has been focused on tissue-type plasminogen activator (t-PA) as a fibrinolytic agent. This article will discuss the unique properties of t-PA and the role of the critical care nurse in providing the safe delivery of t-PA.