Morphological changes in the brain during experimental hyponatraemia. Do vasopressin and gender matter?

Hyponatraemia is the most common electrolyte balance disorder occurring in hospitalized patients. The disease results frequently from inappropriate secretion of vasopressin (SIADH). It has been evidenced that the brain consequences of hyponatraemia are more dramatic in young females than in men or postmenopausal women. Since both vasopressin and oestrogen have been reported to inhibit ion fluxes essential for the adaptation of the brain to the lowering of serum sodium concentration, we sought to study the effect of acute and chronic hyponatraemia or hyponatraemia associated with vasopressin on brain morphology in male and female rats. Hyponatraemia was induced with vasopressin (AVP) or with desmopressin (dDAVP) in 12 male and 12 female adult Wistar rats for either 3 hours (acute) or 3.5 days (chronic). The brains of the animals with diagnosed hyponatraemia were fixed in 10% formalin and, following the standard procedure, stained with haematoxylin and eosin. Acute hyponatraemia resulted in white matter oedema with no obvious differences between genders or between groups with AVP- or dDAVP-induced hyponatraemia. Although in chronic hyponatraemia most neurons and astrocytic nuclei appeared to be normal, some neurons were swollen or ischaemic ("dark" neurons) and astrocytes showed a weak reaction. The most spectacular differences between males and females were found in the appearance of blood vessels. Swollen endothelial cells were observed more frequently in female than in male brains and in AVP- than in dDAVP-induced hyponatraemia. The widened Virchow-Robin spaces indicated perivascular oedema and blood-brain barrier damage. The results point to limited vascular adaptation to AVP-associated hyponatraemia in female gender.

Morphological changes and selective loss of motoneurons in the lumbar part of the spinal cord in a rat model of familial amyotrophic lateral sclerosis (fALS).

Morphological alterations and the course of changes in motoneuron counts were studied by light microscopy (cresyl violet staining) in the L2/L3 region of the spinal cord of hemizygotic transgenic rats carrying the amyotrophic lateral sclerosis-associated mutant human gene for Cu,Zn superoxide dismutase (hSOD1G93A) and of their non-transgenic littermates. In 60-day old transgenic rats, a few ischaemic-looking alpha-motoneurons and occasional vacuolization and accumulation of tigroid in some of the cells were apparent. On day 93 of life more distinct cellular pathology was found in transgenic rats, including moderate gliosis, neuronophagy of alpha-motoneurons, and occasional neuronophagy of gamma-motoneurons. In 120-day-old transgenic rats, abundant gliosis and profound neuronophagy of alpha-motoneurons were observed combined with occasional neuronophagy of other cells. Some loss of alpha-motoneurons was also apparent in 120-day-old non-transgenic littermates of the transgenic rats. No difference in alpha-motoneuron and gamma-motoneuron counts was found between the rats on day 60 of life (early presymptomatic stage of the model disease in the transgenic rats). At 93 days of age (late presymptomatic stage), alpha-motoneuron count, but not gamma-motoneuron count, tended to be lower (p=0.06) in the transgenic rats. On day 120 of life (symptomatic stage), alpha-motoneuron count in the transgenic rats was about half that in their nontransgenic littermates (p<0.001); at this time point the relative decline in alpha-motoneuron number in the former was 57% (day 120 versus day 60; p<0.001). A smaller decline in alpha-motoneuron count was also found in nontransgenic rats (day 120 vs day 60: 24%, p<0.05); this was not associated with the emergence of neurological symptoms or distinct changes in the cell morphology of the spinal cord region studied.

Changes in the distribution of sugar receptors in blood vessels and cell elements of rat brain caused by photochemically induced focal ischaemia.

The lectin technique was applied to the histochemical studies of glycoconjugates comprising membranes of capillary endothelial cells and other cellular elements of the CNS. In the studies we used the following lectins: Concanavalin A (Con A), Bandeirea simplicifolia agglutinin (BS-I), Helix pomatia agglutinin (HPA), Ricinus communis agglutinin (RCA-120), Wheat germ agglutinin (WGA). We noticed changes in the localisation of the glycoconjugates, which are the result of cerebral ischaemia caused by focal irradiation of the left hemisphere of the brain after the previous intravenous injection of control animals with Rose bengal. The described changes seem to be the result of disturbances of the functioning of the blood-brain barrier, which was previously described (Gadamski et al. 2001). In this study, however, we have shown morphological and histochemical changes, which lead to the translocation of examined glycoconjugates within the appearing necrosis areas, around them and in the regions significantly distant from them. This refers to neurones, glial cells and endothelia of brain vessels. So we have described a clear diminution of Con A and HPA-positive receptors from neocortical and hippocampal neurones. The Con A receptors appeared however in morphologically changed, contracted capillaries and HPA receptors in macrophages and reactive cells of necrosis areas. In these areas the BSI-I receptors also appeared and additionally labelled astrocytes in the hippocampus and oligodendrocytes in the corpus callosum. The endothelial glycoconjugates visualised by RCA-120 and WGA also showed weakening of the histochemical reaction in the CNS vascular network and appeared in phagocytes and reactive astrocytes. The focal brain ischaemia induced this way, leading to disturbances in localisation and accumulation of the specific sugar receptors revealed by the lectin technique, determines the histochemical expression of the postischaemic changes in CNS.