Myelin-reactive T-cells are activated by traumatic spinal cord injury (SCI) in rodents and humans. Despite the historical association of these cells with experimental and clinical neuropathology, recent data suggest a neuroprotective role for myelin-reactive T-cells. Because of the biological and therapeutic implications of these findings, we attempted to reproduce the original neuroprotective vaccine protocols in a model of rat SCI. Specifically, MBP-reactive T-cell function was enhanced in SCI rats via passive or active immunization. Locomotor function was assessed using a standardized locomotor rating scale (Basso-Beattie-Bresnahan scale) and was correlated with myelin and axon sparing. The functional and anatomical integrity of the rubrospinal pathway also was analyzed using the inclined plane test and anatomical tract tracing. MBP-immunized rats exhibited varying degrees of functional impairment, exacerbated lesion pathology, greater rubrospinal neuron loss, increased intraspinal T-cell accumulation, and enhanced macrophage activation relative to SCI control groups. These data are consistent with the conventional view of myelin-reactive T-cells as pathological effector cells.

https://www.jneurosci.org/content/jneuro/24/15/3752.full.pdf

Passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats.

Accumulating evidence suggests that activation of the immune system in the central nervous system (CNS) after trauma protects the CNS from damage propagation and facilitates regeneration. Studies by our group have shown that passive transfer of autoimmune T cells specific to myelin basic protein (TMBP) can protect injured neurons in the rat CNS from secondary degeneration. In this study, we investigated the effects of TMBP treatment on the local immune response (by B cells and macrophages) and on the expression of neurotrophic factors after crush injury of the rat optic nerve. Systemic injection of activated TMBP caused an increase in the accumulation of macrophages/microglia and B cells in the injured nerve, which was greater than that seen in the injured optic nerves of untreated animals. This accumulation was accompanied by a transient, but massive, increase in the expression of neurotrophic factors. Immunocytochemical analysis demonstrated differential expression of neurotrophins by resident astrocytes and by infiltrating B cells, T cells, and macrophages. Because postinjury neuronal survival and maintenance are known to be affected by neurotrophins, our findings point to a possible contribution of a neurotrophin-related mechanism to the protective effect conferred by T cell-mediated autoimmunity on injured neurons.

Autoreactive T cells induce neurotrophin production by immune and neural cells in injured rat optic nerve: implications for protective autoimmunity

https://www.cell.com/trends/immunology/pdf/S1471-4906(10)00092-X.pdf

B cells and autoantibodies: complex roles in CNS injury

The immunological response to traumatic brain injury

Endothelium, choroidal epithelium, and arachnoid exclude plasma proteins from most parts of the mammalian central nervous system (CNS). Nerve roots, in contrast, have per- meable capillaries and permeable pia-arachnoid sheaths. Diffusion of plasma proteins into the cerebrospinal fluid is probably prevented by slow bulk flow along a pressure gradient from the subarachnoid space into the veins of the roots. In nerves, the perineurium prevents diffusion of proteins from the epineurium into the endoneurium. Capillaries within fascicles are permeable to macromolecules, though less so than the microvessels of roots and ganglia. Endoneurial vascular permeability is lowest in rats and mice, but even in these species albumin is normally present in the extracellular spaces around the nerve fibers. The so-called blood-nerve barrier is not equivalent to the blood-brain barrier. Capillaries in sensory and sympathetic ganglia are fully permeable to macromolecules, and extravasated protein is in contact with neuronal cell bodies and neurites. An impenetrable perineurium surrounds each ganglion, but serves no obvious purpose when the ves- sels inside are as permeable as those outside. The enteric nervous system lacks a perineurium, and the neurons in its avascular ganglia and tracts are exposed to extracellular fluid formed by per- meable vessels in adjacent tissues of the gut. The reasons for excluding macromolecules from some parts of the nervous system are obscure. Carrier-mediated transport, which maintains a constant supply of ions, glucose, and other metabolites to cells in the CNS, would be impossible if larger molecules could diffuse freely. Presumably the metabolic needs of ganglia are adequately met by exchange vessels similar to those of nonnervous tissues. Most of the CNS is protected from exog- enous toxic substances that bind to plasma proteins. Peripheral neurons and glial cells are damaged by some such substances because of the lack of blood-tissue barriers. o 1996 Wiley-Liss, Inc.

Stefan J

Papers

Studies of immunologic reactions after brain injury. II. Antibodies against brain tissue lipids after blunt head injury in man.

Studies of immunologic reactions after brain injury. I. Antibodies against brain tissue lipids after experimental injury of the brain in rabbits.

Study of immune reactions following brain injury