Search

The evidence that BDNF is involved in neuroprotection, neuronal repair and recovery after traumatic brain injury (TBI) is substantial. We have previously shown that the polymorphism of the human BDNF gene predicts cognitive recovery and outcome following penetrating TBI. The distribution of expression of BDNF and its receptors after penetrating TBI has not been investigated. In this study we examined the expression of these genes in a rat model of penetrating TBI. The injury is produced by a controlled penetration of a 2mm thick needle-shaped object, which is accelerated with a pellet from an air gun. We used in situ hybridization and investigated the mRNA expression of BDNF and its receptors: the full-length and the truncated TrkB and p75(NTR), from 1 day to 8 weeks following penetrating TBI. In addition, the protein level of BDNF in frontal cortex and hippocampus was measured by reverse phase protein microarray (RPPM). The mRNA expression of BDNF and its receptors decreased in the hippocampus in the border zone ipsilateral to the injury while there was an increase in mRNA expression at the contralateral side. The increase in BDNF mRNA expression in the hippocampus was sustained for 2 weeks following injury, with the highest expression noted in the CA3 cell layer. Furthermore, the protein analysis by RPPM showed increased levels of BDNF in the frontal cortex and the hippocampus up to 2 weeks after TBI. At 8 weeks following injury there was an intense labeling of the truncated TrkB receptor and the p75(NTR) in the area surrounding the cavity. Our study is the first report on the expression of BDNF and its receptors following penetrating TBI and suggests that their expression is altered long after the acute phase of injury. Further studies are needed to investigate if the late expressions of these receptors are beneficial or deleterious. In either case it indicates the possibility to influence the recovery after brain injury during the chronic phase and the development of treatments that may improve the outcome of TBI patients., (© 2013 Published by Elsevier B.V.)

Neuropeptide Y (NPY)-like immunoreactivity was examined by fluorescence immunohistochemistry in rat sciatic neuromas, L5 dorsal root ganglias (DRGs) and L5 dorsal roots 1-3 weeks after chronic nerve injury. Anterograde tracing demonstrated that a large number of NPY-positive neuroma fibers were sensory. These fibers were mostly large diameter axons, in line with the finding that a majority of NPY-immunoreactive neurons in the DRG were medium- to large-sized neurons which showed immunoreactivity to the neurofilament antibody RT 97. In dorsal roots NPY immunoreactivity was strong after sciatic neuroma formation. Dorsal rhizotomy and ligation, on the other hand, did not induce NPY immunoreactivity at any of the sites examined.

The spinal pia mater receives a rich innervation of small sensory and autonomic axons via the ventral roots. In the present study this pathway was interrupted by the transection of the L7 ventral root in young kittens. The animals were killed 12-18 months postoperatively. It was observed that the pia mater adjacent to the divided ventral root contained large numbers of myelinated axons. We suggest that these axons represent sprouts which had reached the pia mater by retrograde growth from the neuroma on the ventral root. Some of these aberrant pial axons ended blindly in the pia mater. Abnormal terminal-like swellings were observed along pial blood vessels. Fibers with diameters exceeding 11 microns were observed. Many fibers had an internodal spacing below 100 microns and the maximum value was only about 300 microns. Thus, motor axons which are forced to grow into a foreign territory show a maldevelopment which is more obvious with regard to nodal spacing than to fiber diameter.

Staphylococcus aureus plays an important role as a bacterial pathogen after traumatic injury. The majority of isolated strains produces alpha-toxin, a 33-kDa protein, with membrane-damaging and lethal effects. The central nervous system (CNS) has been considered as the possible target for the lethal action of this toxin. A transfer of alpha-toxin across an intact blood-brain barrier (BBB) is however unlikely. The aim of the present study was to determine if alpha-toxin is accumulated in CNS regions which lack the BBB function. The distribution of alpha-toxin after intravascular injections, in normal mice and rats as well as in rats subjected to ventral root replantation, was assessed using immunogold technique. The results show that, although alpha-toxin does not cross the BBB, alpha-toxin-like immunoreactivity could be detected in the area postrema and at the optic nerve-retinal junction. Extravasation of alpha-toxin was also shown to occur in the spinal cord even 22 months after ventral root replantation. This finding suggests that axon regeneration after ventral root replantation takes place in a macromolecular environment which is totally different from the normal CNS. The implications of vascular spread of alpha-toxin to regions devoid of BBB function are discussed in relation to the bacterial infections which might complicate severe spinal injuries.