Central nervous system: a modified immune surveillance circuit?

Immune surveillance in the central nervous system (CNS) was considered impossible because: (i) the brain parenchyma is separated from the blood circulation by the blood-brain barrier (BBB); (ii) the brain lacks lymphatic drainage and (iii) the brain displays low major histocompatibility complex class II (MHCII) expression. In this context, the BBB prevents entry of immune molecules and effector cells to the CNS. The absence of lymphatic vessels avoids CNS antigens from reaching the lymph nodes for lymphocyte presentation and activation. Finally, the low MHCII expression hinders effective antigen presentation and re-activation of T cells for a competent immune response. All these factors limit the effectiveness of the afferent and efferent arms necessary to carry out immune surveillance. Nevertheless, recent evidence supports that CNS is monitored by the immune system through a modified surveillance circuit; this work reviews these findings.

Neuroprotective effect of silymarin in a MPTP mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease secondary to the loss of dopaminergic neurons in the substantia nigra. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces in mice and primates histopathological changes similar to PD in humans. A common feature of PD and MPTP models is neuronal death and dopamine depletion. Silymarin is a complex of flavonolignans derived from the seeds of the plant Silybum marianum and has mainly antioxidant, anti-inflammatory, cytoprotective and neuroprotective effects. In order to explore whether silymarin has a neuroprotective effects in a mouse model of PD we determined the concentration of striatal dopamine by HPLC, the number of apoptotic cells by in situ Tunel assay and the number of tyrosine hydroxylase positive neurons by immunohistochemistry in substantia nigra of vehicle-treated, silymarin-treated, MPTP-intoxicated and MPTP-silymarin treated C57BL/6J male mice. MPTP (30 mg/kg) and silymarin doses (25, 50, 100, 200, 250, 300 or 400mg/kg) were administered intraperitoneally once daily for five consecutive days. Silymarin treatment showed a non-monotonic dose-response curve and only 50 and 100mg/kg doses preserved dopamine levels (62% and 69%, respectively) after MPTP intoxication. Additionally, 100mg/kg silymarin treatment significantly diminished the number of apoptotic cells and preserved dopaminergic neurons in the substantia nigra of MPTP-intoxicated mice. These results show the neuroprotective properties of 100mg/kg silymarin and may be of interest in the treatment of PD.

Regulatory T cells in central nervous system: in health and disease.

Regulatory T cells participate in several immune responses including autoimmune reactions inducing self-tolerance, tumor immunity, transplantation tolerance and microbial infection. Nevertheless regulatory T cells actions seem to be different when they are in the central nervous system (CNS), since they interact with resident cells of the CNS, according to the particular conditions elicited in this compartment. This review focuses on the role of regulatory T cells in health, autoimmune and other CNS diseases, pointing out their interactions with resident CNS cells.