Blood glucose and ischemic brain damage.

The effect of hyperglycemia on ischemic brain damage was studied in a rat model of incomplete ischemia. Incomplete ischemia was produced by permanent occlusion of one (either left or right) common carotid artery (CCA). Hyperglycemia was induced by intraperitoneal injection of 50% glucose, and same volume of physiological saline was injected in the controls 40 min before CCA ligation. Serum glucose level, at the time of vessel ligation, was 33.3 mMol/L. After CCA ligation, the rats were allowed to wake up and survive for upto 1 month. Perfusion-fixed brains were embedded in paraffin, subserially sectioned, and stained with haematoxylin-eosin/cresyl violet. Brain from sham-operated animals showed no damage neurons. Only mild neuronal damage was observed in saline pre-treated rats in CA1 area. Histological examination 24 h after CCA occlusion revealed ischemic neuronal cell damage to be more extensive in hyperglycemic rats. Neuronal damage was found in the major brain structures vulnerable to several insults. Some of those damaged neurons recovered well, but presence of some damaged neurons at 1 month of recovery suggesting delayed recovery. The results indicate that increased blood glucose level (hyperglycemia) during brain ischemia exaggerates structural alterations and leads to delay in recovery.

Effects of anodal polarization on protein kinase Cgamma (PKCgamma) in the rat brain.

An anodal direct current of 0.3 microA or 30.0 microA was unilaterally applied for 30 min or 3 hr to the surface of the sensorimotor cortex of rats, and the effects of anodal polarization on protein kinase C (PKCgamma) activity were examined. The brains were processed by means of immunocytochemistry using the monoclonal antibody 36G9 raised against purified PKCgamma. In sham-operated animals, PKCgamma-like-immunoreactivity (PKCgamma LI) was noted in neuronal cytoplasm, as well as in processes in the cerebral cortex and in the hippocampus. Anodal polarization with 3.0 miroA for 30 min resulted in a pronounced increase in the number of PKCgamma-like-positive neurons in accordance with the intensity of immunostaining in the cerebral cortex, and an increase in the polarized hemispheres was highlighted by repeated applications of the currents. Polarization with 0.3 microA for 3 hr also increased the PKCgamma LI, but 0.3 microA for 30 min or 30.0 microA for any duration had no effects. The effect of polarization on PKCgamma activity, as evaluated by the intensity of immunostaining and the number of neurons, began to increase 1 h after polarization, peaked at 3 hr and thereafter decreased to the control levels by 72 hr. These results indicated the involvement of the gamma-isoform of PKC in the neurochemical mechanism of long-standing central and behavioral changes induced by anodal polarization.

Cardiac malignant lymphoma in severe combine immunodeficient mice.

Extranodal malignant lymphomas are known to occur with increased frequency in patients with human immunodeficiency virus infection. Although cardiac malignant lymphomas are rare, recently an increasing number of patients with acquired immune deficiency syndrome (AIDS) and cardiac lymphoma have been reported. To clarify the relationship between AIDS and cardiac lymphomas, we used 60 severe combine immunodeficient (SCID) mice as animal models in whom five different types of human lymphoma cell lines were injected. Primary lymphomas at the site of cell line injection developed within 14-30 days in 58 mice. Cardiac malignant lymphoma was detected in 10 cases (17%), among which tumour was macroscopically evident in 2. Tumour was present on the pericardial aspects of the heart extending into the myocardium in most cases, but no intracavitary lesion was observed. In one case, obstructive features were marked near the root of the great vessels by direct pressure of the growth. This study indicates that lymphomas have a predilection to invade the heart in immunocompromised conditions.

Co-localization of c-fos protein and protein kinase C gamma in the rat brain following anodal polarization.

The expression of protein kinase c gamma (PKC gamma) and c-fos protein was examined by means of double labeling in the rat brain in relation to the molecular mechanism of central plastic changes associated with anodal polarization. Under normal, non-polarized condition, approximately 75% of all fos positive neurons in the neocortex were immunopositive for PKC gamma. Conversely, nearly all PKC gamma positive neurons were fos immunopositive. Although both pyramidal and non-pyramidal neurons express both types of protein, the pyramidal cell type represents the vast majority. An anodal direct current of 3.0 microA for 30 min to the surface of the left sensorimotor cortex resulted in a pronounced increase in the intensity of immunoreactivity for both PKC gamma and c-fos protein ipsilateral to the polarization. Approximately, 91% of fos positive neurons in the polarized neocortex was also intensely immunoreactive for PKY gamma. The high degree of codistribution of both transduction proteins in specific neurons following anodal polarization suggests the functional connection between PKY gamma activation and c-fos expression in polarization phenomenon.

Immunocytochemical distribution of gamma isoform of protein kinase C (PKC-gamma) following incomplete ischaemia.

Immunocytochemical distribution of PKC-gamma was examined in rat brain in relation to molecular mechanisms of post-ischaemic neuronal modulation following incomplete ischaemia. Incomplete ischaemia was developed by either permanent occlusion of one common carotid artery (CA) or permanent occlusion of one CA with temporary occlusion of opposite CA. Unilateral CA (UCA) occlusion resulted in a pronounced increase in the intensity of staining and number of PKC-gamma positive neurons in the neocortex ipsilateral to the insult after 3 h. The effect was maximum at 6-12 h and was undetectable after 7 days. CA1 neurons showed an increase immunoreactivity (IR) after 1 day, reached to a peak by 3 days, then reduced to basal levels after 7 days. Bilateral CA (BCA) occlusion showed almost similar changes in the neocortex, but on both sides and short durated. The altered patterns of PKC-gamma IR in the neocortex and hippocampus following CA occlusion may reflect activation and/or down-regulation of PKC-gamma in ischaemic neurons. PKC-gamma may, therefore, potentially play an important role in the post-ischaemic modulation of synaptic efficacy in these neurons and in the neuronal damage following incomplete ischaemia.

Induction of N-methyl-D-asparate receptor mediated c-fos protein in the rat brain by incomplete ischaemia.

The expression of c-fos protein was examined by means of immunocytochemistry in the rat brain following incomplete ischaemia, to elucidate the molecular mechanisms of post-ischaemic neuronal death and of the modulated neurotransmission of surviving neurons. Incomplete ischaemia was produced by permanent unilateral or bilateral common carotid artery (CCA) occlusion. After 1 h of unilateral occlusion, the level of c-fos protein-like nuclear immunoreactivity increased in cortical neurons ipsilateral to the insult, especially in cingulate and piriform cortices. The reactivity peaked at 3-6 h, and was undetectable after 3 days. A number of scattered immunostained neurons in the ipsilateral subiculum, CA 1 and dentate gyrus became visible after 1 day. The effect reached a peak between 1-3 days, then returned to basal levels by 7 days. Bilateral CCA occlusion showed a similar distribution of immunoreactivity, but on both hemispheres. Immunoreactive neurons were more numerous and intensely stained but more transient. The induction of c-fos was completely blocked or reduced by treatment with MK-801. Our results suggest that c-fos expression after CCA occlusion is NMDA receptor mediated, and that it has a specific role in neurons after ischaemic insult.

Carotid artery occlusion causes reversible brain damage in rat.

In order to assess the density and distribution of brain damage after pure focal ischemia uncomplicated by hypotension or hypoxia, ischemia was produced by occlusion of one and/or both common carotid arteries (CCA) temporarily or permanently in the rat, followed by 3 months recovery. The brains were perfusion-fixed with formaldehyde, embedded in paraffin, subserially sectioned, and stained with hematoxylin-eosin/cresyl violet. Mild ipsilateral neuronal damage was observed after unilateral permanent occlusion, but confined only to the hippocampus. Damage of neocortical neurons began to appear after 1 day following bilateral permanent occlusion. Damage was worst over the superolateral convexity of both hemispheres, CA 4 and subiculur neurons; subsequently other sectors of hippocampus and other brain structures were affected. Some damaged neurons in the superficial cortex and CA 1 sector of hippocampus, and almost all in the other regions of brain reverted to normal profile by 3 months of recovery. All brain structures showed normal profiles, except a relative neuronal rarefication in neocortex and CA 1 sector of hippocampus after 3 months of recovery. These results suggests that only CCA occlusion causes partial/incomplete ischemia in the rat brain, where damaging effects are counterbalanced by metabolic and circulatory adjustments.