EFFECT OF HYPOTHERMIA ON BLOOD-BRAIN BARRIER PERMEABILITY FOLLOWING TRAUMATIC BRAIN INJURY IN CHRONICALLY ETHANOL-TREATED RATS

The objective of this study was to investigate the effect of hypothermia on the blood-brain barrier (BBB) disruption caused by traumatic brain injury (TBI) in chronically ethanol-treated rats. BBB permeability was measured using Evans blue (EB) dye. Arterial blood pressure levels of animals in hypothermic groups decreased significantly. The EB dye extravasation into the brain significantly increased in hypothermia and at 6 and 24 h after TBI. In ethanol-treated rats that were subjected to TBI, hypothermia led to a significant decrease in EB dye content in the brain at 24 h but not at 6 h after TBI when compared with TBI alone.     

A POTENT INHIBITOR OF NEURITE OUTGROWTH THAT PREDOMINATES IN THE EXTRACELLULAR MATRIX OF REACTIVE ASTROCYTES

In a model of astrogliosis in vitro, cultured cortical astrocytes were triggered into a functionally reactive state by an immobilized fragment of the β-amyloid peptide. Induced astrocytes produced an extracellular matrix that inhibited the outgrowth of embryonic CNS axons. Within the extracellular matrix deposited by reactive astrocytes, we found an overall increase in the deposition of chondroitin sulphate that accounted for the inhibition. Specifically, we have detected an increased biosynthesis of a small chondroitin/heparan sulphate proteoglycan that is a potent inhibitor of axon outgrowth. We further suggest that this proteoglycan, or related molecules yet to be discovered, may play a role in gliosis-mediated regenerative failure of CNS axons. Copyright © 1996 ISDN.     

Olfactory ensheathing cells induce less host astrocyte response and chondroitin sulphate proteoglycan expression than Schwann cells following transplantation into adult CNS white matter

Both Schwann cells and olfactory ensheathing cells (OECs) create an environment favorable to axon regeneration when transplanted into the damaged CNS. However, transplanted cells can also exert an effect on the host tissue that will influence the extent to which regenerating axons can grow beyond the transplanted area and reenter the host environment. In this study equivalent numbers of Lac-Z-labeled Schwann cells and OECs have been separately transplanted into normal white matter of adult rat spinal cord and the host astrocyte response to each compared. Schwann cell transplantation resulted in a greater area of increased glial fibrillary acidic protein (GFAP) expression compared to that associated with OEC transplantation. This was accompanied by a greater increase in the expression of axon growth inhibitory chrondroitin sulfate proteoglycans (CSPGs) following Schwann cell transplantation compared to OEC transplantation. However, no differences were detected in the increased expression of the specific CSPG neurocan following transplantation of the two cell types. These results mirror differences in the interactions between astrocytes and either Schwann cells or OECs observed in tissue culture models and reveal one aspect of the complex biology of creating regeneration-promoting environments by cell transplantation where transplanted OECs have favorable properties compared to transplanted Schwann cells.     

Activated Macrophages and the Blood–Brain Barrier: Inflammation after CNS Injury Leads to Increases in Putative Inhibitory Molecules

The cellular responses to spinal cord or brain injury include the production of molecules that modulate wound healing. This study examined the upregulation of chondroitin sulfate proteoglycans, a family of molecules present in the wound healing matrix that may inhibit axon regeneration in the central nervous system (CNS) after trauma. We have demonstrated increases in these putative inhibitory molecules in brain and spinal cord injury models, and we observed a close correlation between the tissue distribution of their upregulation and the presence of inflammation and a compromised blood–brain barrier. We determined that the presence of degenerating and dying axons injured by direct trauma does not provide a sufficient signal to induce the increases in proteoglycans observed after injury. Activated macrophages, their products, or other serum components that cross a compromised blood–brain barrier may provide a stimulus for changes in extracellular matrix molecules after CNS injury. While gliosis is associated with increased levels of proteoglycans, not all reactive astrocytes are associated with augmented amounts of these extracellular matrix molecules, which suggests a heterogeneity among glial cells that exhibit a reactive phenotype. Chondroitin sulfate also demarcates developing cavities of secondary necrosis, implicating these types of boundary molecules in the protective response of the CNS to trauma.     

Expression changes of nerve cell adhesion molecules L1 and semaphorin 3A after peripheral nerve injury

The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.