Experimental pneumococcal meningitis causes central nervous system pathology without inducing the 72-kd heat shock protein

We examined whether experimental pneumococcal meningitis induced the 72-kd heat shock protein (HSP72), a sensitive marker of neuronal stress in other models of central nervous system (CNS) injury. Brain injury was characterized by vasculitis, cerebritis, and abscess formation in the cortex of infected animals. The extent of these changes correlated with the size of the inoculum (P less than 0.003) and with pathophysiologic parameters of disease severity, i.e., cerebrospinal fluid (CSF) lactate (r = 0.61, P less than 0.0001) and CSF glucose concentrations (r = -0.55, P less than 0.0001). Despite the presence of numerous cortical regions having morphologic evidence of injury, HSP72 was not detected in most animals. When present, only rare neurons were HSP72 positive. Western blot analysis of brain samples confirmed the paucity of HSP72 induction. The lack of neuronal HSP72 expression in this model suggests that at least some of the events leading to neuronal injury in meningitis are unique, when compared with CNS diseases associated with HSP72 induction.

Shear stress modulates the expression of thrombospondin-1 and CD36 in endothelial cells in vitro and during shear stress-induced angiogenesis in vivo

Binding of thrombospondin-1 (TSP-1) to the CD36 receptor inhibits angiogenesis and induces apoptosis in endothelial cells (EC). Conversely, matrix-bound TSP-1 supports vessel formation. In this study we analyzed the shear stress-dependent expression of TSP-1 and CD36 in endothelial cells in vitro and in vivo to reveal its putative role in the blood flow-induced remodelling of vascular networks. Shear stress was applied to EC using a cone-and-plate apparatus and gene expression was analyzed by RT-PCR, Northern and Western blot. Angiogenesis in skeletal muscles of prazosin-fed (50 mg/l drinking water; 4 d) mice was assessed by measuring capillary-to-fiber (C/F) ratios. Protein expression in whole muscle homogenates (WMH) or BS-1 lectin-enriched EC fractions (ECF) was analyzed by Western blot. Shear stress downregulated TSP-1 and CD36 expression in vitro in a force- and time-dependent manner sustained for at least 72 h and reversible by restoration of no-flow conditions. In vivo, shear stress-driven increase of C/F in prazosin-fed mice was associated with reduced expression of TSP-1 and CD36 in ECF, while TSP-1 expression in WMH was increased. Down-regulation of endothelial TSP-1/CD36 by shear stress suggests a mechanism for inhibition of apoptosis in perfused vessels and pruning in the absence of flow. The increase of extra-endothelial (e.g. matrix-bound) TSP-1 could support a splitting type of vessel growth.

Myocardial infarction and post-traumatic stress disorder: frequency, outcome, and atherosclerotic mechanisms

BACKGROUND: Post-traumatic stress disorder (PTSD) may develop in the aftermath of an acute myocardial infarction (MI). Whether PTSD is a risk factor for cardiovascular disease (CVD) is elusive. The biological mechanisms linking PTSD with atherosclerosis are unclear. DESIGN: A critical review of 31 studies in the English language pursuing three aims: (i) to estimate the prevalence of PTSD in post-MI patients; (ii) to investigate the association of PTSD with cardiovascular endpoints; and (iii) to search for low-grade systemic inflammatory changes in PTSD pertinent to atherosclerosis. METHODS: We located studies by PubMed electronic library search and through checking the bibliographies of these sources. RESULTS: The weighted prevalence of PTSD after MI was 14.7% (range 0-25%; a total of 13 studies and 827 post-MI patients). Two studies reported a prospective association between PTSD and an increased risk of cardiovascular readmission in post-MI patients and of cardiovascular mortality in combat veterans, respectively. In a total of 11 studies, patients with PTSD had increased rates of physician-rated and self-reported cardiovascular diseases. Various cytokines and C-reactive protein were investigated in a total of seven studies suggesting that PTSD confers a pro-inflammatory state. CONCLUSIONS: Increasing evidence suggests that PTSD specifically related to MI develops considerably frequently in post-MI patients. More research is needed in larger cohorts applying a population design to substantiate findings suggesting PTSD is an atherogenic risk factor and to understand better the suspected behavioural and biological mechanisms involved.

Exhaustion is associated with reduced habituation of free cortisol responses to repeated acute psychosocial stress

We investigated the association between exhaustion and the habituation of free cortisol responses to repeated stress exposure. The study comprised 25 healthy male subjects (38-59 years) who were confronted three times with the Trier Social Stress Test. Mean cortisol responses showed the well-known general habituation effect. A two-way interaction day by exhaustion (p<0.05) indicated that mean cortisol responses vary across stress sessions depending on the extent of exhaustion. Linear regression revealed a negative dose-response relationship between exhaustion and the degree of habituation (p<0.02). We identified 19 individuals showing a response habituation (negative slope) and 6 individuals showing a response sensitization over the three sessions (positive slope) with the latter reporting higher exhaustion scores. It might be hypothesized that impaired habituation to repeated exposure to the same stressor could reflect a state of increased vulnerability for allostatic load. Absence of normal habituation might be one potential mechanism how exhaustion relates to increased disease vulnerability.

Acute stress reactions in the first 3 weeks postpartum: A study of 219 parturients

OBJECTIVES: There is increasing research on posttraumatic stress (PS) 4-6 weeks and 3 months postpartum, but, there are no data on acute stress reactions (ASR) in the first 3 weeks postpartum, i.e. the potential precursors of PS. However, ASR may have long-term effects, e.g., on a subsequent pregnancy without having manifested as PS in the meantime. We propose: (i) to describe the patterns of ASR after childbirth, (ii) to explore differences between women with normal and traumatogenic ASR, and (iii) to provide data on the early detection of traumatogenic ASR 2 and 3 weeks postpartum. STUDY DESIGN: Intra-event variables (relationship with caregivers, overall birth experience, and dissociative experiences, as well as obstetric variables) were assessed 48-96h. postpartum, as were ASR (by means of the Impact-of-Event Scale IES) in weeks 1, 2, and 3 postpartum. According to research on PS the upper 33%-range of ASR in weeks 2 and 3 was defined as 'traumatogenic'. RESULTS: Normal ASR in week 1 are at a level which in non-obstetric trauma-situations is considered as the upper range of low stress or lower range of medium distress. ASR decline constantly from week 1 to week 3. However, high ASR in week 1 do not drop faster than do low ones, thus indicating a prolonged stress reaction in women with high ASR in week 1. Low ASR (IES-scores <10) and high ASR (IES-scores >20) in week 1 are highly predictive for normal ASR, and traumatogenic ASR in weeks 2 and 3, respectively. Medium ASR (IES-scores 10-20) in week 1 are of uncertain predictive value for stress reactions in weeks 2 and 3 and have to be re-assessed at that time. CONCLUSIONS: Clinical screening for ASR appears to be helpful in detecting women with a compromised ability to process childbirth-related stress. The association between ASR and long-term development should be further explored.