Experimental isovolemic haemodilution-induced augmentation of carotid blood flow and oxygen transport through graded carotid stenoses.

The effect of haemodilution without volume expansion (isovolemic haemodilution) was assessed with respect to blood flow and oxygen transport across stenotic lesions of progressive severity in the dog carotid artery. As the mean haematocrit (Hct) was reduced from 40 +/- 1% (+/- SEM) to 32 +/- 0% (p less than 0.001), reductions in vascular resistance were significant across the 90% (p less than 0.001) and 95% (p less than 0.0003) relative carotid stenoses. Isovolemic haemodilution reduced fresh blood viscosity significantly by 27 +/- 3% (p less than 0.001) and 42 +/- 4% (p less than 0.001) at the low shear rates of 10 sec-1 and 1 sec-1 which are typical of low-flow states. Following a 20% reduction in Hct 30 to 35% increase (p less 0.001) in carotid blood flow occurred at non-critical degrees of stenosis while a mean 83% increase (p less than 0.001) occurred at the highly critical 95% relative stenosis. Oxygen transport after a 22% decrease in blood haemoglobin was significantly increased by 28% (p less than 0.01) at the 95% relative stenosis level. These data provide a physiologic rationale for the beneficial effects of haemodilution in acute cerebral ischaemia, cerebral vasospasm and cerebral revascularization or carotid endarterectomy.     

Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801.

In order to study the involvement of NMDA-receptor activation in brain development, rat pups were chronically treated with the non-competitive NMDA antagonist MK-801 during the neonatal period. We recorded the cortical EEG at various vigilance states throughout the treatment period. Spectral analysis of the EEG showed reduced power in the delta (delta) frequency range (1.5-4 Hz) during quiet sleep and less power in the theta (theta) range (4-7 Hz) during REM-sleep in MK-801 animals than in controls. No significant differences were found for the total time spent in each of the different vigilance states. We conclude that chronic MK-801 treatment probably causes a developmental retardation in state-related brain activities.     

Transneuronal degeneration of thalamic neurons following deafferentation: quantitative studies using [3H]thymidine autoradiography.

Transneuronal degeneration of thalamic neurons following partial deafferentation was studied using [3H]thymidine autoradiography. Timed-pregnant female Sprague-Dawley rats received systemic injections of [3H]thymidine on embryonic day (E) 13, 14 and/or 15. On the day of birth, pups were anesthetized by hypothermia and subjected to unilateral enucleation, unilateral removal of the inferior colliculus or sham lesion. Animals were sacrificed on postnatal day 10 or 30 and the brains processed for autoradiography. Material from sham-lesioned animals demonstrates that neurons destined for the dorsal lateral geniculate nucleus (LGd) undergo final mitoses on E13, 14 and 15. Neurons in the ventral medial geniculate nucleus (MGv) undergo final mitoses on E13 and 14. Thirty days following neonatal unilateral eye removal, the contralateral LGd displays a loss of approximately 30-35% of [3H]thymidine labeled neurons. Neonatal unilateral removal of the inferior colliculus results in a loss of approximately 30-40% of labeled neurons in MGv. For both LGd and MGv, shorter survival times reveal less severe cell loss. Late generated (E15) LGd neurons show less severe loss following enucleation than do earlier generated neurons. These results document the degree of cell loss in sensory thalamic nuclei following deafferentation and demonstrate that [3H]thymidine autoradiography provides a useful quantitative method for assessing anterograde transneuronal cell loss in targeted populations of neurons in the developing central nervous system.     

An in vivo study of the ontogeny of long-term potentiation (LTP) in the CA1 region and in the dentate gyrus of the rat hippocampal formation.

The influences of stimulus intensity, intratrain frequency, and number of trains were studied for their effects on the development of long-term potentiation (LTP) in the hippocampal formation. LTP was analyzed with full input-output curves for population spike (PS) amplitudes (PS-LTP) calculated from responses elicited in the CA1 region and in the dentate gyrus by monosynaptic activation. A standardized protocol employing a sequence of stimuli was devised to systematically compare LTP in the dentate gyrus to that in the CA1 region in rats of various ages ranging from postnatal day (PN) 6 to adults (PN 60). In adult animals, the degrees of LTP were comparable in the dentate gyrus and CA1 region for the 3 stimulus strengths studied (intensity just subthreshold for PS, intensity giving 1/4 maximal PS, and intensity giving 1/2 maximal PS). LTP developed at different rates in the two regions, reaching adult values about two weeks after birth in CA1 but about 3 weeks after birth in the dentate gyrus. We postulate that differences in the rate of development in CA1 and in the dentate gyrus are related to the later neurogenesis of dentate granule cells and also possibly to a later functional maturation of N-methyl-D-aspartate (NMDA) receptor-channel complexes on these cells.     

Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical characterisation of Toxoplasma antigen, infiltrates and major histocompatibility complex gene products

The experimental infection of immunocompetent and immunodeficient athymic mice with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to study the ensuing encephalitic process by use of histological and immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+ and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post-infection because of a generalized toxoplasmosis with predominant involvement of the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation of class I and II major histocompatibility complex (MHC) gene products. Class I antigen was widely expressed on microglial cells and astrocytes. Class II antigen was only expressed on microglial cells despite a considerable astrogliosis. Our results indicate a differential expression of MHC-determined antigens on brain cells in acute and chronic murine Toxoplasma encephalitis.     

Are haemostatic and fibrinolytic parameters predictors of preeclampsia in pregnancy-associated hypertension?

The plasma levels of several haemostatic and fibrinolytic parameters were measured before and after delivery in 61 hypertensive pregnant women of whom 22 developed preeclampsia, and compared to the results obtained in 42 normal pregnant women. In the two last weeks before delivery (D less than or equal to -15) tPA antigen, PAI-1 activity, vWF:Ag/FVIII:C ratio, ATIII activity and platelet count were found to be significantly different in the hypertensive pregnant women with and without preeclampsia. Combined all together, an association of three of these five parameters were found to be pathological (i.e.:tPA:Ag greater than or equal to 19 ng/ml, PAI-1 activity greater than or equal to 58 IU/ml, vWF:Ag/FVIII:C ratio greater than or equal to 2.6, ATIII activity less than or equal to 73%) in none of the hypertensive women without preeclampsia and in only 35% of the preeclamptic group. A positive correlation was demonstrated between vWF:Ag/FVIII:C ratio and tPA:antigen levels suggesting that both tPA and vWF:Ag could be considered as early indicators of a possible micro angiopathy occurring in preeclampsia. However, due to the high dispersion of the results, it appears that the investigated haemostatic and/or fibrinolytic criteria give only presumptive arguments before assigning risk for preeclampsia development among hypertensive pregnant women.     

Modulation of mild bleeding disorder during remissions and exacerbations of Graves' disease

A patient with Graves' disease had a symptomatic thrombocytopathy during periods of remission. When euthyroid, she noticed bruising, petechiae, and epistaxis. Hemostatic abnormalities included prolongation of the bleeding time by aspirin, reduced platelet retention (a second-phase defect), and abnormal thrombin-induced aggregation and serotonin release. When hyperthyroid, bleeding symptoms resolved, and platelet function returned to normal. These observations suggest that mild bleeding disorders may be influenced either directly or indirectly by thyroid hormone levels.