Brain infections as well as peripheral challenges to the immune system lead to an increased production of interleukin-1beta (IL-1b), a cytokine involved in leukocyte-mediated breakdown of the blood-brain barrier. The effects of IL-1b have been reported to depend on whether the route of administration is systemic or intracerebral. Using 50-day-old male rats, we compared the effects of IL-1b on brain γ-glutamyl transpeptidase (GGT; an enzymatic marker of brain capillary endothelium) at 2, 24 and 96 h after either an intravenous (i.v.) injection of 5 μg IL-1β or an intracerebroventricular (i.c.v. - lateral ventricle) infusion of 50 ng IL-1β. When the i.v. route was used, the GGT activity underwent small but significant changes; decreasing in the hippocampus 2 h after the i.v. injection, increasing 24 h later and returning to control levels at 96 h. No significant changes in the hippocampal GGT activity were observed at 2 and 24 h following the i.c.v. infusion. The GGT activity in the hypothalamus remained unchanged regardless of the route of IL-1b administrations. Similar changes in GGT activity were revealed histochemically. The labeling was found mainly in the capillary bed, the changes being most evident in the hippocampal stratum radiatum and stratum lacunosum-moleculare. A transient increase in GGT activity at 24 h, together with a less sharp delineation of GGT-stained vessels, may reflect IL-1b induced increased turnover of glutathione and/or oxidative stress, that may in turn, be related to altered permeability of the blood-brain barrier in some neurological and mental disorders, including schizophrenia.
A unifying picture to the hermeneutical approach to schizophrenia is given by combining the philosophical and the experimental/computational approaches. Computational models of associative learning and recall in the cortico-hippocampal system helps to understand the circuits of normal and pathological behavior.