Fluid percussion brain injury exacerbates glutamate-induced focal damage in the rat

The role of glutamate-mediated neuronal damage in neurotrauma remains controversial. The cerebral levels measured in patients by microdialysis are sufficient to kill neurons in culture, but not in the intact brain of the normal rat. A synergistic effect between excitatory amino acid-mediated damage and other posttrauma mechanisms must therefore be proposed, if glutamate is indeed a significant cause of posttraumatic brain damage. The presence of such a synergistic mechanism was therefore investigated by combining in vivo glutamate perfusion and fluid percussion injury (FPI). Twenty-four adult male Sprague Dawley rats were randomly assigned to three groups: (1) vehicle (n = 9): mock cerebrospinal fluid (CSF) perfusion plus FPI; (2) glutamate + FPI (n = 9): 0.1 M glutamate intracortical perfusion plus FPI; and (3) glutamate without FPI (n = 6). After preparation for central FPI, at a moderate level of injury (2 +/- 0.5 atm), glutamate or mock CSF perfusion was performed via a CMA/12 microdialysis probe (3 mm). Animals were then perfusion fixed, under deep anesthesia, after 3-h survival, for volumetric histopathology. The glutamate perfusion + FPI group (2.42 +/- 1.63 mm3) produced a significantly bigger lesion than mock CSF perfusion + FPI (0.063 +/- 0.41 mm3) and glutamate perfusion alone (1.00 +/- 0.47 mm3). Traumatic brain injury thus seems to enhance glutamate-mediated brain damage, and this may be due to qualitative changes induced in ion channels and receptors, such as the N-methyl-D-aspartate channel, after shear injury.     

Gait pattern in patients with spastic diplegic cerebral palsy who underwent staged operations

Fifteen patients with spastic diplegic cerebral palsy (CP) were monitored for a mean length of 9.5 years after they underwent staged operations and were evaluated by gait analysis, including joint motion in the sagittal plane and the ground reaction force (GRF) in three dimensions. Results showed an increased hip flexion (132%) at midstance, a reduction of peak knee flexion (PKF) during swing (45%) accompanied by an augmented time of PKF during swing (50%), and an increased dorsiflexion of the ankle during swing (293%) as well as its time during the gait cycle, in comparison with normal values. Moreover, significant decreases of the vertical GRF at the terminal stance and the forward and backward GRF were present. Additionally, it was found that a bilateral popliteal angle < 20 degrees is acceptable in spastic CP. Staged operations gave unpredictable results in the correction of contracture of the hamstrings, the Achilles tendon, and the iliopsoas. The authors are convinced that gait analysis is useful in evaluating these patients and enhances the results of operative treatment, and they have since changed their approach toward multilevel simultaneous corrections.     

Injury induces neuropsin mRNA in the central nervous system

We have shown that neuropsin is expressed in the neurons of the limbic system in the adult mouse. After the central nervous system was injured by incision or intraperitoneal kainate injection, neuropsin mRNA was induced in the peri-lesioned region. The cells in which neuropsin mRNA was induced were localized mainly in axon fiber pathways and closely associated to proteolipid protein (PLP) mRNA expressing oligodendrocytes.     

Morphological and functional demonstration of rat dura mater mast cell-neuron interactions in vitro and in vivo

The effects of changes in temperature on primary and secondary endings of isolated cat muscle spindles were investigated under ramp-and-hold stretches and different degrees of pre-stretch. Temperature-induced alterations of the discharge frequency were compared over a temperature range of 25–35°C. Both primary and secondary endings responded to warming with increasing discharge frequencies when the spindle was pre-stretched by 5–10% of its in situ length. The following differences between the temperature effects on primary and secondary endings were observed: (1) The temperature coefficients (Q₁₀) obtained from the discharge frequencies during the dynamic and static phase of a stretch were similar for endings of the same type, but they were larger in primary endings (range of Q₁₀: 2.3–3.3; mean: 2.9) than in secondary endings (range of Q₁₀: 1.6–2.2; mean: 2.0); (2) With primary endings, but not with secondary endings, the temperature sensitivity (imp s⁻¹ °C⁻¹) was larger during the dynamic phase than during the static phase of a stretch; (3) In primary endings, the fast and slow adaptive components occurring in the discharge frequency during the static phase of a stretch clearly increased with warming while in secondary endings, the slow decay was less affected, and the fast decay showed no change; (4) In relaxed spindles, the excitatory effect of warming was overlaid by a strong inhibitory effect as soon as the temperature exceeded about 30°C, resulting in an abrupt cessation of the background activity in most secondary endings, but not usually in primary endings. In general, warming induced an enhanced stretch sensitivity in both types of ending, and additionally an inhibitory effect that is obvious only in secondary endings of relaxed spindles. The different effects of temperature on the discharge frequency of primary and secondary afferents are assumed to be caused by different properties of their sensory membranes.     

Cholecystokinin/opioid interactions

Cholecystokinin (CCK) acts as an anti-opioid peptide. The mechanisms of CCK-opioid interaction under normal and pathological conditions were examined with various techniques. Nerve injury induces upregulation of CCK mRNA and CCK2 receptors in sensory neurons. The involvement of CCK in spinal nociception in normal and axotomized rats was examined. The CCK2 receptor antagonist CI-988 did not reduce spinal hyperexcitability following repetitive C-fiber stimulation in normal or axotomized rats, suggesting that CCK is probably not released from injured primary afferents. With in vivo microdialysis intravenous (i.v.) or intrathecal (i.t.) morphine increased the extracellular level of CCK in the dorsal horn in a naloxone reversible manner. Morphine also released CCK after axotomy, but not during carrageenan-induced inflammation. In contrast, K(+)-stimulation failed to increase extracellular levels of CCK in axotomized rats, but did so in inflamed rats. Double-coloured immunofluorescence technique revealed partial co-localization between CCK-like immunoreactivity (LI) and mu-opioid receptor (MOR)-LI in superficial dorsal horn neurons. The presence of MOR in CCK containing neurons suggests a possible direct influence of opioids on CCK release in the spinal cord. Axotomy, but not inflammation, induced a moderate decrease in CCK- and MOR-LI in the dorsal horn. I.v. morphine further temporarily reduced CCK- and MOR-LIs in axotomized, but not in normal or inflamed, rats. While the effect of morphine on CCK-LI can be interpreted as the result of increased CCK release, the effect on MOR-LI may be related to changes in the microenvironment of the dorsal horn induced by nerve injury.     

A photothrombotic ring stroke model in rats with or without late spontaneous reperfusion in the region at risk

This study aimed at developing a dual setup of the photothrombotic ring stroke model with or without late spontaneous reperfusion in the region at risk and to explore the morphological consequences. The exposed crania of adult male Wistar rats were subjected to a ring-shaped laser-irradiation beam (o.d. 5.0 mm, 0.35 mm thick) for 2 min simultaneously with intravenous erythrosin B (17 mg/kg) infusion. Transcardial carbon-black perfusion revealed that a laser intensity of 0.90 W/cm(2) resulted in late, that is, starting at 72 h, spontaneous reperfusion, whereas the lowest laser intensity that produced lack of reperfusion at 7 days post-irradiation was 1.84 W/cm(2). Laser-Doppler flowmetry showed prompt cortical cerebral blood flow (cCBF) reduction both in the ring lesion and region at risk (12% and 25% of control values) after high-intensity irradiation; these reduced flow values were more rapid and pronounced than in the low-intensity irradiation setup as previously shown. The high- compared with low-intensity irradiation setup produced more frequent occurrence of thrombi in the ring-lesion region and a larger ischemic cortical lesion with a more rapid pace of ischemic cellular changes in the ring-lesion region and the region at risk. The region at risk transformed into pannecrosis in the high-intensity, but recovered morphologically in the low-intensity irradiation setup. This dual photothrombotic setup with or without spontaneous reperfusion enables the study of events related to ischemic cell survival or death in an anatomically predefined region at risk.     

Tenascin-C in the cochlea of the developing mouse

Tenascin-C is a glycoprotein of the extracellular matrix that acts in vitro as both a permissive and a nonpermissive substrate for neurite growth. We analyzed, by immunocytochemistry, the distribution of tenascin-C along neural growth pathways in the developing mouse cochlea. In the spiral lamina, tenascin-C coexists in a region where nerve bundles arborize. In the organ of Corti, tenascin-C lines the neural pathways along pillar and Deiters' cells before and during the time of nerve fiber ingrowth. By embryonic day 16, tenascin-C is abundant on the pillar side of the inner hair cell but does not accumulate on the modiolar side until about birth, a time after the arrival of afferent fibers. The synaptic zones beneath outer hair cells are strongly labeled during the time when early events in afferent synaptogenesis are progressing but not during the time of efferent synaptogenesis. At the age when most neural growth ceases, tenascin-C immunoreactivity disappears. Faint tenascin-C immunolabeling of normal hair cells, strong tenascin immunolabeling in pathological hair cells of Bronx waltzer (bv/bv) mice, and staining for beta-galactosidase, whose gene replaces tenascin in a "knockout" mouse, indicate that hair cells supply at least part of the tenascin-C. The changing composition of the extracellular matrix in the synaptic region during afferent and efferent synaptogenesis is consistent with a role for tenascin in synaptogenesis. The presence of tenascin-C along the growth routes of nerve fibers, particularly toward the outer hair cells, raises the possibility that growth cone interactions with tenascin-C helps to guide nerve fibers in the cochlea.