Effect of 21-aminosteroid on extracellular energy-related metabolites and amino acids after compression injury of rat spinal cord.

We evaluated in a rat model of severe spinal cord compression the effect of the 21-aminosteroid tirilazad on extracellular levels of energy metabolites and amino acids, until 3 h after injury. The compound was given i.v. 30 min before injury (3 mg/kg) and hourly thereafter (1.5 mg/kg). The findings were compared with previously reported effects of methylprednisolone. Both treated and untreated rats with spinal cord compression showed, at 10 min after injury, a five- to sixfold elevation of extracellular lactate above the preinjury level. There was no significant difference for lactate, pyruvate or lactate/pyruvate ratio between the treated and untreated injured groups at any time point after trauma. Glutamate was significantly elevated both in treated and untreated injured rats for 20 min after trauma. The mean glutamate level was lower in animals treated with 21-aminosteroid. However, there was no statistically significant difference between the treated and untreated rats at any time after trauma. There was no statistically significant difference between the groups for aspartate, serine, glutamine, histidine, glycine, threonine, taurine, alanine and tyrosine. In conclusion our findings indicate that, in the injured spinal cord, methylprednisolone and the 21-aminosteroid have differences and similarities, regarding their effects on energy and amino acid metabolism. The lowering of the lactate and arginine levels early after trauma seen with methylprednisolone pretreatment was absent after 21-aminosteroid pretreatment. However, the mean extracellular level of glutamate was lower with both methylprednisolone and 21-aminosteroid after injury, although the difference was not statistically significant between treated and untreated rats.

Traumatic brain injury in rat produces changes of beta-amyloid precursor protein immunoreactivity.

beta-Amyloid precursor protein immunoreactivity (APP) was studied after a mild compression contusion trauma to rat parietal cortex. Neurones in the periphery of the cortical lesion, i.e. tissue subjected to shear stress, showed markedly reduced immunoreactivity 1 and 3 days after injury. Numerous axons in the ipsilateral subcortical white matter and thalamus became immunoreactive. At 21 days, small rounded profiles appeared in the neuropil of the damaged cortex and in the thalamus. Thus, traumatic brain injury appears to induce several types of APP changes. The accumulation in neuronal processes is probably caused by disturbed axonal transport induced by trauma. Since APP is assumed to be excitoprotective, modulating intracellular Ca2+ responses, the decreased immunoreactivity noticed in the periphery of the lesion may render the neurones in this region more vulnerable to secondary injury mechanisms.

Positron emission tomography and computed tomography in differential diagnosis between recurrent or residual glioma and treatment-induced brain lesions.

In previous studies of supratentorial gliomas with positron emission tomography (PET) and computed tomography (CT), high uptakes of L-methyl-11C-methionine (11C-L-methionine) were found even in astrocytomas without blood-brain barrier defects as judged by CT or 68Ga-EDTA PET. In a number of patients examined after radiation therapy, there were no consistent changes in the high uptake values. In the present investigation PET and CT were compared with regard to their abilities to visualize and delineate recurrent tumors and treatment-induced brain defects and to differentiate between them. The study was undertaken on four patients who were long-term survivors after treatment for high-grade gliomas. For PET, 11C-L-methionine and 68Ga-EDTA were used. In two patients recurrent/residual tumors appeared considerably larger with 11C-L-methionine PET than with CT or 68Ga-EDTA PET. In one patient, no signs of recurrence were seen with any of these three methods, and in a fourth patient, whose condition was clinically stable, the findings at PET with 11C-L-methionine were non-specific. In areas corresponding to the surgical parenchymal defects, the 11C-L-methionine uptake and, except in one case, the local blood volume was markedly reduced. PET with 11C-L-methionine thus has a potential for distinguishing between postoperative brain lesions and tumor recurrence with a higher accuracy than CT.

Evaluation of the toxicity of subarachnoid clonidine, guanfacine, and a substance P-antagonist on rat spinal cord and nerve roots: light and electron microscopic observations after chronic intrathecal administration.

Clonidine has been reported to produce analgesia in man after epidural and intrathecal administration. In the present investigation the alpha 2-adrenoceptor agonists clonidine and guanfacine were tested to evaluate their potential spinal neurotoxic effects. Rats were injected daily for 14 consecutive days via catheters implanted in the intrathecal space. Clonidine was administered at a dose of 1.63 micrograms or 16.3 micrograms, and guanfacine at 16.3 or 75 micrograms. After perfusion with a buffered 3% glutaraldehyde solution, the spinal cords and nerve roots were taken for neuropathological analysis using light and electron microscopy. Compared to animals injected with 0.9% saline, clonidine and guanfacine gave rise to no detectable neurotoxic changes in the doses employed. An additional group of rats had intrathecal injections of a substance P-antagonist (D-Arg1, D-Trp7,9, Leu11)-substance P (spantide) with known neurotoxic effect as a test of the histotechnical methods used. Degenerative lesions, with a preference for the ventral horns, were consistently present in the grey matter of the cord in these animals. We conclude that the absence of detectable changes in rats given clonidine and guanfacine is probably a real expression of the low degree of toxicity for these compounds on rat spinal cord and nerve roots and not an artifact of the sensitivity of the histotechniques applied. The doses of clonidine administered were considerably greater than those reported to produce clinical greater than those reported to produce clinical analgesia.