The effects of total-body irradiation on the permeability of rat striatal blood-brain barrier (BBB) to [3H]alpha-aminoisobutyric acid (AIBA) and [14C]sucrose were investigated using the microdialysis technique. Seven days, 3 and 6 weeks, and 3, 5, and 8 months after gamma exposure at a dose of 4.5 Gy, no modification of the permeability to both [3H]AIBA and [14C]sucrose was observed. But, in the course of the initial syndrome, we observed a significant but transient increase in the BBB permeability to the two markers between 3 and 17 h after exposure. A secondary transient "opening" of the BBB to [14C]sucrose was noticed about 28 h following irradiation without the corresponding increase in BBB permeability to [3H]AIBA. On the contrary, the transport of [3H]AIBA through the BBB was decreased between 33 and 47 h postradiation. In conclusion, our experiments showed early modifications of BBB permeability after a moderate-dose whole-body exposure. Confirmation of these results with other tracers, in another experimental model or in humans, would have clinical applications for designing appropriate pharmacotherapy in radiotherapy and treatment of accidental overexposure.

Background: Cytokine mRNA quantification is widely used to investigate cytokine profiles, particularly in small samples. Real-time polymerase chain reaction is currently the most reliable method of quantifying low-level transcripts such as cytokine and cytokine receptor mRNAs. This accurate technique allows the quantification of a larger pattern of cytokines than quantification at the protein level, which is limited to a smaller number of proteins.

Recovery from radiation-induced (RI) bone marrow aplasia depends on appropriate cytokine support. The early effects of exogenous cytokines at the hematopoietic stem and progenitor cell (HSPC) level following irradiation are still largely unknown, especially those of survival factors such as stem cell factor (SCF) and Flt-3 ligand (FL). This study was aimed at A) clarifying Fas/Fas-Ligand (Fas-L) implication in RI apoptosis of CD34 + cells and B) assessing the capacity of a combination of cytokines to mitigate RI apoptosis in HSPCs in vitro. We showed that most of in vitro gamma-irradiated CD34 + HSPCs incubated in a medium devoid of cytokines underwent progressive apoptosis-related changes from 6 h (i.e., decreased CD34 antigen expression, Annexin V binding); then Fas/Fas-L coexpression occurred from 10 h on. A strong DNA fragmentation, as assessed by TUNEL assay and propidium iodide staining, was observed at 24 h. Within a 2.5-to 6-Gy dose range, the RI apoptotic process finally led to 97% CD34 + cell death within 48 h with a complete loss of functionality. Unirradiated cells incubated in the same conditions displayed a significantly reduced apoptotic pattern. The early addition of a combination of SCF, FL, thrombopoietin, and interleukin 3 (4F) after cell irradiation prevented 15% (2.5 Gy) and 12% (4 Gy) of HSPCs, respectively, from RI apoptosis, whereas these cytokines used as single factors were inefficient. Furthermore, irradiated HSPCs (2.5 Gy) incubated with 4F in a serum-free culture system for seven days proliferated, giving rise to an increase in the number of total cells (× 5.6-fold) and CD34 + cells (× 4.2-fold) and to megakaryocytic and granulomonocytic precursors. These results show that the prevention of apoptosis in in vitro irradiated HSPCs depends on an early combination cytokine support. These data suggest that the early therapeutic administration of anti-apoptotic cytokines may be critical for preserving functional HSPCs from in vivo radiation damage.

Summary Chronic stress is known to induce immunological disorders. In the present study we examined the consequences of chronic restraint stress on the immune response to tetanus toxin in mice. We investigated the repartition of subsets of lymphoid cells in blood and spleen, the functional ability of lymphocytes to proliferate and to produce cytokines, and antibody titres against tetanus toxin following stress. We report discordance of the stimulation index of lymphocytes in the restraint group: the proliferating rate severely decreased following stimulation with a relevant antigen, whereas it increased with mitogen. Thus, we report a decrease in cytokine production with relevant antigen (interferon‐γ and interleukin‐10), without a T helper type 1 and 2 secretion imbalance. Moreover, we observed an alteration in the humoral response, including a delay in isotype maturation and an immunoglobulin G1/G2a imbalance.

No abstract