The interaction between the CNS and the systemic immune system is delicate, being limited by the presence of the blood brain barrier (BBB), which renders the CNS immune homeostasis in a dormant self-tolerant state (1). Selective permeability of the BBB plays a crucial role in regulating the entry of specific molecules into the CNS and excluding most macromolecules from passing into the brain (2, 3). This unique feature of the BBB also prevents leakage of neurotransmitters into the circulation. After sustaining a TBI, breakdown of the BBB frequently follows (4), instigating the entry of typically non-permeating molecules into the brain and thus altering the normal neural functions of the CNS (5). Likewise, the BBB compromise causes macromolecules
…show more content…
For instance, cytokines, which have proinflammatory roles in peripheral organs, exhibit essential roles in regulating the synaptic plasticity and activity within the CNS (7-9), such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) (10). Besides, although activation of the complement system and release of its components is well-known to trigger inflammatory response in many body organs, including the brain itself, experimental evidence reveals a potential role of some of these molecules in enhancing myelin and oligodendrocytes function, such as terminal C5b-9 complexes (11). Other complement proteins were also proven to maintain a neuroprotective function through supporting development and maturation of glia and neurons, and preventing CNS toxicity and cellular apoptosis. Those include C3, C3a, C5, C5a and the membrane attack complex (MAC) …show more content…
Hence, it either expresses unique antigens that are not realized in other body tissues or other common antigens but to an appreciable degree in other tissues. The CNS-reactive antibodies that may be present in the circulation are generally harmless to the host. Nevertheless, in the context of TBI and upon breakdown of the BBB under pathologic conditions, an autoantibody-mediated pathology may occur (1, 6). In post-CNS trauma, B-lymphocytes are assumed to contribute to part of the injury encountered in addition to the systemic disturbances (14) by releasing specific neural autoantibodies and several other systemic antibodies, such as serum rheumatoid factor (RF) in cases of SCI (15). The underlying process behind this is differentiation of B-lymphocytes via antigen-specific T cells, which occurs once former cells encounter their cognate antigens, into antibody-secreting plasma cells (16, 17), where immunoglobulin genes undergo class-switch recombination and somatic hypermutation (6). In CNS injury, and upon disruption of the BBB, neural cells get exposed to the circulating antibodies and serum proteins. These molecules, particularly autoantibodies, produce their cytotoxic effects on neurons and glial cells through activation of the complement system, as previously mentioned, after which cytokine-mediated
For instance, cytokines, which have proinflammatory roles in peripheral organs, exhibit essential roles in regulating the synaptic plasticity and activity within the CNS (7-9), such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) (10). Besides, although activation of the complement system and release of its components is well-known to trigger inflammatory response in many body organs, including the brain itself, experimental evidence reveals a potential role of some of these molecules in enhancing myelin and oligodendrocytes function, such as terminal C5b-9 complexes (11). Other complement proteins were also proven to maintain a neuroprotective function through supporting development and maturation of glia and neurons, and preventing CNS toxicity and cellular apoptosis. Those include C3, C3a, C5, C5a and the membrane attack complex (MAC) …show more content…
Hence, it either expresses unique antigens that are not realized in other body tissues or other common antigens but to an appreciable degree in other tissues. The CNS-reactive antibodies that may be present in the circulation are generally harmless to the host. Nevertheless, in the context of TBI and upon breakdown of the BBB under pathologic conditions, an autoantibody-mediated pathology may occur (1, 6). In post-CNS trauma, B-lymphocytes are assumed to contribute to part of the injury encountered in addition to the systemic disturbances (14) by releasing specific neural autoantibodies and several other systemic antibodies, such as serum rheumatoid factor (RF) in cases of SCI (15). The underlying process behind this is differentiation of B-lymphocytes via antigen-specific T cells, which occurs once former cells encounter their cognate antigens, into antibody-secreting plasma cells (16, 17), where immunoglobulin genes undergo class-switch recombination and somatic hypermutation (6). In CNS injury, and upon disruption of the BBB, neural cells get exposed to the circulating antibodies and serum proteins. These molecules, particularly autoantibodies, produce their cytotoxic effects on neurons and glial cells through activation of the complement system, as previously mentioned, after which cytokine-mediated