The gamut of blood flow responses coupled to spreading depolarization in rat and human brain: from hyperemia to prolonged ischemia.

Cortical spreading depolarizations (SD) have been shown to occur frequently in patients with aneurysmal subarachnoid hemorrhage (SAH) and are associated with delayed ischemic brain damage. In animal models the link between SD and cell damage is the microvascular spasm coupled to the passage of SDs, resulting in spreading ischemia. Here we compared the hemodynamic changes induced by SD between human and rat cerebral cortex. Specifically, we addressed the question, whether the full spectrum of regional cerebral blood flow (rCBF) responses to SD is found in the human brain in a similar fashion to animal models. SDs were identified by slow potential changes in electrocorticographic recordings and the rCBF response profiles and magnitudes were analyzed. We found a large variability of rCBF changes concomitant to SDs in rat and in human recordings. The spectrum ranged from normal hyperemic responses to prolonged cortical spreading ischemia with intermediate forms characterized by biphasic (hypoemic-hyperemic) responses. The bandwidths of rCBF responses were comparable and the relative response magnitudes of hypo- and hyperperfusion phases did not differ significantly between rats and humans. The correspondence of the rCBF response spectrum to SD between human and animal brain underscores the importance of animal models to learn more about the mechanisms underlying the early and delayed pathological sequelae of SAH.

Modeling pediatric head trauma: mechanisms of degeneration and potential strategies for neuroprotection.

We have developed a model for head trauma in infant rats in an attempt to study mechanisms of neurodegeneration in the developing brain and were able to morphologically characterize two distinct types of brain damage. The first type or primary damage evolved within 4 hrs after trauma and occurred by an excitotoxic mechanism. The second type or secondary damage evolved within 6-24 hrs and occurred by an apoptotic mechanism. Primary damage remained localized to the parietal cortex at the site of impact. Secondary damage affected distant sites such as the cingulate/retrosplenial cortex, subiculum, frontal cortex, thalamus, hippocampal dentate gyrus and striatum. Histological evidence of delayed cell death was preceded by decrease of bcl-2- in conjunction with increase of c-jun-mRNA-levels, already evident at 1 hr after trauma. Increase of CPP32-like activity and elevated concentrations of oligonucleosomes in affected brain regions represented additional findings to indicate that this secondary disseminated degenerative reaction is apoptotic in nature. At the age of 7 days, secondary apoptotic damage was more severe than primary excitotoxic damage, but its severity declined with increasing age. In 7-days-old rats, NMDA antagonists protected against primary excitotoxic damage but increased severity of secondary apoptotic damage whereas the free radical scavenger SPBN, the tumor necrosis factor (TNF) inhibitor pentoxifylline and the antioxidant N-acetylcystein mitigated apoptotic damage. These findings demonstrate that in the developing rat brain apoptosis and not excitotoxicity determines neuropathologic outcome following head trauma. Whereas radical scavengers and TNF-inhibitors may prove useful in treatment of pediatric head trauma, great caution should be applied in regards to the use of NMDA antagonists because of the inherent risk of apoptosis promotion.

Subtypes of depression, efficacy, and the Depressive Experiences Questionnaire.

The purpose of our study was to reanalyze the Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976, 1979) and to evaluate relationships between the questionnaire's factors and other construct-related measures, the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961) and the Edwards Personal Preference Schedule (Edwards, 1959). We argue that composite scores derived from this study's principal components analysis are more interpretively useful than the original factor scales reported by Blatt et al. (1976; Blatt, Quinlan, Chevron, McDonald, & Zuroff, 1982). Correlational evidence reported in this study does not support the Dependency and Self-Criticism factors as adequate representations of anaclitic and introjective depression (Blatt, 1974). The third DEQ factor scale, Efficacy, as revised for this study, demonstrated moderate to strong associations with other personality measures.

Arginine vasopressin response to hypertonicity in hypertension studied by arginine vasopressin assay in unextracted plasma.

OBJECTIVE: To investigate whether plasma osmolality (Posm)-plasma arginine vasopressin (PAVP) response relationships with particular characteristics of sensitivity, gain or response pattern (linear/non-linear) occur more frequently in hypertensive than normotensive subjects. DESIGN: Analysis of Posm-PAVP curves observed in individual normotensive and hypertensive subjects rather than whole groups was considered appropriate for the described objective. METHODS: A sensitive and precise radioimmunoassay of PAVP in unextracted plasma was developed. Posm was raised in 11 normotensive and 19 hypertensive subjects by infusion of NaCl solution (0.86 mol/l, i.v.), and PAVP assayed at intervals. Best-fitting linear and non-linear equations for the Posm-PAVP relationship were established by computer. RESULTS: The mean rise in osmolality, blood pressure and blood volume was similar in the two groups. Hypertensive subjects showed a tendency towards higher rates of response (pmol AVP/l per mosm per kg) at Posm greater than 290 mosm/kg, leading to a non-linear response pattern compared with the normotensive subjects. CONCLUSIONS: The enhanced PAVP responses found in the hypertensive subjects at Posm greater than 290 mosm/kg may reinforce vascular and central nervous pathogenetic mechanisms.