Plasma osmolality and brain water content in a rat glioma model

Little is known about how intravenous fluids influence peritumoral edema formation. This experiment was designed to determine, in a rat glioma model, whether changes in plasma osmolality alter water content, as assessed by specific gravity (SpGr), in normal and neoplastic cerebral tissue. Cells cultured from an ethylnitrosourea-induced rat glioma were stereotactically implanted into the right striatum of Fischer 344 rats. A tumor growth interval of 21 days was allowed. In a second experiment, rats underwent a 60-second cortical freeze injury followed by 24 hours' recovery. In both experiments, rats were assigned to one of three groups: hypotonic (100 ml/kg of 0.2 mol/L NaCl in H2O, intraperitoneally; resultant plasma osmolality approximately 268 mOsm/kg); isotonic (no treatment; plasma osmolality approximately 298 mOsm/kg); or hypertonic (10 ml/kg of 1.0 mol/L NaCl in H2O, intraperitoneally; plasma osmolality approximately 342 mOsm/kg). Thirty minutes after fluid injection, regional SpGr was determined using a kerosene-bromobenzene gradient. In subsets of rats, the tissue morphology and blood-brain barrier permeability of Evans blue dye were assessed. Tissue within the freeze lesion was stained by Evans blue dye with sharp demarcation. Evans blue dye did not stain gliomatous tissue, and central necrosis was not histologically evident. In isotonic rats, glioma SpGr was reduced (1.0411 +/- 0.0012 g/ml) relative to the contralateral striatum (1.0437 +/- 0.0008 g/ml; P < 0.001). Despite this, a strong linear relation was observed for SpGr and plasma osmolality in both neoplastic and normal tissue. Within the freeze lesion in isotonic rats, SpGr was severely reduced (1.0335 +/- 0.0008 g/ml; P < 0.0001) compared with contralateral frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacological properties of homomeric and heteromeric GluR1o and GluR3o receptors

Homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits GluR1o and GluR3o were expressed in Spodoptera frugiperda (Sf9) insect cells. Membranes containing the recombinant receptors showed a doublet of bands of the expected size (99-109 kDa) after western immunoblotting which was shifted to a single band upon deglycosylation. In (R,S)-[3H]AMPA binding experiments, high expression was seen (Bmax = 0.8-3.8 pmol/mg protein) along with high affinity binding to a single site (Kd, nM+/-S.D.): GluR1o, 32.5+/-2.7; GluR3o, 23.7+/-2.4; GluR1o + GluR3o, 18.1+/-2.9. The pharmacological profiles of these receptors resembled that of native rat brain AMPA receptors: AMPA analogues > L-glutamate > quinoxaline-2,3-diones > kainate. In the Xenopus oocyte expression system we had previously shown that the agonist (R,S)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionate (ACPA) exhibited an 11-fold selectivity for GluR3o vs. GluR1o. In this study, it was found that ACPA has 3-fold higher affinity at homomeric GluR3o and heteromeric receptors than at homomeric GluR1o, suggesting that its efficacy and/or desensitisation properties are different at GluR1o vs. GluR3o.     

The decerebrate human: associative learning

Phasic changes in cardiac reactivity to innocuous stimuli, presented in a sensory disparity paradigm, were used to evaluate habituation and learning processes in five decerebrate subjects. Three subjects showed systematic changes over trials in the pattern of cardiac response to simple auditory or visual stimuli, indicative of habituation. In addition, tests for associative learning were given after repeated presentations of two paired stimuli. The appearance of a marked cardiac orienting response, to the unpredictable omission of the second stimulus, documented the development of a conditioned association in these same three subjects. One additional subject failed to show a consistent pattern of response to the stimuli, and another demonstrated a consistent response which was not subject to habituation. Overall, these findings support the view that learning processes are not solely the product of the cerebral hemispheres, but reflect general integrative features of the human neuraxis.     

Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen

Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) alpha/beta lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTalpha- and LTbeta-deficient mice. Treatment of adult mice with antagonists of LTalpha1beta2 also leads to decreased BLC expression. These findings indicate that LTalpha1beta2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTalpha-, and LTbeta-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus-induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTalpha1beta2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.