Regional study of spinal alpha 2-adrenoceptor densities after intraspinal noradrenergic-rich implants on adult rats bearing complete spinal cord transection or selective chemical noradrenergic denervation.

One of the challenges of restorative neuronal transplantation in the CNS of mammals is the appropriate integration of grafted cells in the host circuitry. One key parameter is the specific influence of grafted cells upon corresponding receptors. In order to test this issue on the lesioned spinal cord of adult rats, two models of spinal cord denervation were used: the first one consisted of a complete transection 1 week prior to an intraspinal transplantation of embryonic locus coeruleus (LC) primordia cell suspension; the second one was a chemical destruction of the spinal noradrenergic (NA) system 1 month prior to a similar transplantation. Five weeks after transplantation, spinal sections were processed for autoradiographic quantification of alpha 2-adrenoceptor binding sites densities. In most regions, alpha 2-adrenoceptor densities remained comparable or higher than before graft; interestingly, in lumbar dorsal horn, lumbar intermediate zone and sacral distal dorsal horn of transected-grafted rats, they returned to control level. Results are discussed in relation to the parallel study performed concerning alpha 1-adrenoceptors.

Transplantation of embryonic noradrenergic neurons in two models of adult rat spinal cord injury: ultrastructural immunocytochemical study.

The synaptic connections established by grafted noradrenergic (NA) neurons into the lesioned adult rat spinal cord were analysed using immunocytochemistry at the electron microscopic level. An embryonic cell suspension of the locus coeruleus region from E-13 rat embryos was transplanted into the spinal cord following either: (1) spinal cord transection or (2), partial selective denervation by 6-hydroxy dopamine (6-OH DA). One month after grafting, the NA-neurons established, in the two models, an innervation pattern similar to that found in the intact spinal cord. In both models, the transplanted NA-immunoreactive neurons formed extensive synaptic contacts with dendrites, spines and perikarya. The proportion of axodendritic and axospinous contacts was inverse in the two models. The first model thus reproduced more closely the normal synaptic pattern prefering dendritic targets, which could correspond to a better integration of the graft. In the second model, a partially NA-denervated spinal cord, there existed a competition between residual intrinsic and grafted neuron-derived fibres, which presumably affects synaptogenesis. In conclusion, the present study illustrate the complexity of cell interations conducting to the formation of a specific circuitry. Recognition phenomenon are likely modulated by space constraints, which ultimately shape-up the geometry of synaptic contacts.

Intraspinal noradrenergic-rich implants reverse the increase of alpha 1 adrenoceptors densities caused by complete spinal cord transection or selective chemical denervation: a quantitative autoradiographic study.

This study examined, in the adult rat, whether the intraspinal transplantation of a cell suspension of embryonic day (ED)13 rat locus coeruleus primordia was able to normalize the lesion-induced increase of spinal alpha 1-adrenoceptors. Two experimental models of spinal denervation were studied. The first model consisted of a complete spinal cord transection (thoracic vertebrae level T8-T9) and 1 week later, the cell suspension was transplanted below the section; the second one was obtained by a selective chemical lesion of the noradrenergic (NA) system and one month later, the cell suspension was implanted at the same level as in transected rats. Five weeks after grafting, all animals were sacrificed and spinal cord tissue sections were processed for immunohistochemical detection of noradrenaline or for quantification of alpha 1-adrenoceptors binding sites densities using [3H]prazosin as a ligand. After 6-OHDA lesion, as well as caudally to the transection, a significant increase by 21% (P < 0.01) to 68% (P < 0.001) of alpha 1-adrenoceptors densities was detected. The implantation of embryonic NA neurons into the denervated spinal cord led to a reversal of the lesion-induced increase of spinal alpha 1-adrenoceptors, five weeks later. Moreover, this reversal seems to be more effective after mechanical than after chemical denervation.

Normal distribution of alpha 2-adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: a quantitative autoradiographic study.

The distribution of alpha 2 (alpha 2)-adrenoceptors along cervical, thoracic, lumbar, and sacral segments of the spinal cord of normal rats has been studied by quantitative autoradiography using the specific alpha 2-antagonist [3H]rauwolscine as a ligand. In addition, the influence of noradrenergic (NA) denervation [obtained either by complete transection of the spinal cord at vertebrae level T8-T9 or by selective lesion of NA spinal cord system carried out by intracisternal injection of 6-hydroxydopamine (6-OHDA)] on eventual variations of alpha 2-adrenoceptor density at spinal cord target cells was studied in parallel. In control rats, the quantitative analysis of alpha 2-adrenoceptor densities revealed the presence of these receptors throughout the whole gray matter with a preferential location in the superficial dorsal horn. This pattern was the same at all rostro-caudal levels of the cord and appeared very well correlated with the distribution of NA terminals revealed by immunohistochemistry, particularly in the superficial layers of the dorsal horn. After total transection of the spinal cord (caudally to the section) and 6-OHDA-induced lesion, an increase of alpha 2-adrenoceptor density was mainly observed within the distal dorsal horn thus evidencing supersensitivity in this area, while modifications were not detectable in other regions of the spinal gray matter, except at the lumbar level where other dorsal, central, and intermediate zones were significantly enriched.

Normal distribution of alpha-1-adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: a quantitative autoradiographic study.

The distribution of alpha 1 (alpha 1)-adrenoceptors along the different segments of the spinal cord (cervical, thoracic, lumbar, and sacral) of normal rats has been studied by quantitative autoradiography using the specific alpha 1-antagonist [3H]Prazosin as a ligand. In addition, the influence of noradrenergic (NA) denervation [obtained either by complete transection of the spinal cord at vertebrae level T8-T9 or by selective lesion of NA spinal cord system carried out by intracisternal injection of 6-hydroxydopamine (6-OHDA)] on eventual variations of alpha 1-adrenoceptor density at spinal cord target cells was studied in parallel. In control rats, the quantitative analysis of alpha 1-adrenoceptor densities revealed a widespread distribution of these receptors along all segments of the spinal cord with a similar pattern in the various subregions of gray matter studied. This distribution of alpha 1-adrenoceptors was quite well correlated with the distribution of NA terminals, when referring to previous descriptions by immunohistochemistry. After 6-OHDA lesion, as well as caudally to the transection, a significant increase of alpha 1-adrenoceptor densities was observed in all spinal subregions thus evidencing supersensitivity. These results suggest that NA may act in the spinal cord, at least partly, via alpha 1-adrenoceptors and that the expression of these receptors could be influenced by NA dysfunction, as demonstrated here through the effects observed in lesioned animals.

Prophylaxis of bacterial infections after bone marrow transplantation. A randomized prospective study comparing oral broad-spectrum nonabsorbable antibiotics (vancomycin-tobramycin-colistin) to absorbable antibiotics (ofloxacin-amoxicillin).

Bacterial infection is a common complication after allogeneic bone marrow transplantation. It is related to the toxic effects of the conditioning regimen on mucosal surfaces, to bone marrow aplasia and to the prolonged lymphopenia with immune deficiency that lasts for several weeks after bone marrow transplantation. We have performed a prospective randomized study comparing two methods of prophylaxis. Group I (OA) received a combination of ofloxacin 400 mg/day and amoxicillin 20 g/day; group II (VTC) received the oral nonabsorbable antibiotics vancomycin 450 mg/day, tobramycin 450 mg/day and colistin 4.5.10(6) units daily, from day -15 to 15 days after discharge from laminar air flow (LAF) rooms. All patients were nursed in LAF rooms with a strict isolation procedure and sterile water and food. They were evaluated daily for clinical symptoms, and bacterial culture samples were taken from the throat, stools and blood twice weekly. Forty-four patients were randomized, 22 entered in group I (OA) and 22 in group II (VTC). There were no differences between the two groups in age (mean 33 years, range 11-54), sex, diagnosis and mean duration of agranulocytosis (21.8 days, range 10-49). Seven patients were excluded because of the selection of a resistant bacteria, 5 were in group I (OA), and 2 were in group II (VTC). The mean duration of fever was 9.2 +/- 7.1 days in group I (OA) and 13.7 +/- 6.8 days in group II (VTC; p = 0.05). There were no significant differences between the two groups in graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS)