Therapeutic potential of treatment with the flavonoid rutin after cortical focal ischemia in rats

AbstractFlavonoids have known anti-inflammatory and antioxidative actions, and they have been described as neuroprotective and able to reduce damage in CNS diseases. We evaluated the action of the flavonoid rutin in an animal model of focal cortical ischemia induced by unilateral thermocoagulation of superficial blood vessels of motor (M1) and somatosensory (S1) primary cortices. Ischemic rats were submitted to daily injections (i.p.) for five days, starting immediately after induction of ischemia. We tested two doses: 50mg/kg or 100mg/kg of body weight. Sensorimotor tests were used to evaluate functional recovery. Bioavailability in plasma was done by chromatographic analysis. The effect of treatment in lesion volume and neurodegeneration was evaluated 48h and 72h after ischemia, respectively. We observed significant sensorimotor recovery induced by rutin, and the dose of 50mg/kg had more pronounced effect. Thus, this dose was used in further analyses. Plasma availability of rutin was detected from 2h to at least 8h after ischemia. The treatment did not result in reduction of lesion volume but reduced the number of degenerated neurons at the periphery of the lesion. The results suggest rutin as an efficient drug to treat brain ischemia since it was able to promote significant recovery of sensorimotor loss, which was correlated to the reduction of neurodegeneration in the periphery of cortical injury. Increasing studies with rutin and other flavonoids might give support for further clinical trials with these drugs

Blocking IgE with L-glutamic acid analogs as an alternative approach to allergy treatment

IgE-mediated allergic diseases have increased in the last decades. The most prevalent allergens from these seeds are Ric c1 and Ric c3, isoforms of 2S albumin. These allergenic proteins cross-react with allergens from peanut, shrimp, fish, corn, gramineous, house dust, and tobacco. The usual allergy treatment employs antihistaminic, immunotherapies and, omalizumab (Xolair)-based anti-IgE therapy. However, antihistaminics relieve symptoms, and the high cost of omalizumab limits its use for continuous treatment. We propose an alternative immunotherapeutic approach, denoted “IgE-blockage” by L-glutamic acid or modified-glutamic acid. Six compounds, D-glutamic acid, L-glutamic acid, N-methyl-L-glutamic acid, N-acetyl-L-glutamic acid, N-(4-nitrobenzoyl)-L-glutamic acid, and N-carbamyl-L-glutamic, were tested as a blocker. To evaluate motor coordination and the sedative/hypnotic activity of L-glutamic acid, a rota-rod test and a thiopental sodium-induced sleeping test were used. The compounds, L-glutamic acid and L-nitrobenzoyl glutamic acid, were the most active compounds to block the interaction of castor allergens with IgE. These compounds also prevent cross-responses with allergens from food sources and inhalants that cross-react with them. In the sleeping test, the groups that received L-glutamic acid at doses of 10 and 30 mg/kg had a sleeping time similar to the vehicle control group. No changes in the animals' behavior were observed and there was no difference between the L-glutamic acid groups and the vehicle control groups in the rota-rod test. L-glutamic acid and L-nitrobenzoyl glutamic acid can used as IgE blocker to prevent allergic diseases. DOI: http://dx.doi.org/10.5281/zenodo.768610

Removal of the cortical projections alters expression of NOS in the different cell types of the superficial layers of the superior colliculus in rats

Nitric oxide has several biological roles and nitric oxide synthase (NOS) is expressed in the nervous system, and co-localizes with NADPH-diaphorase. The superficial layers of the superior colliculus (SC), which receive retinal and cortical inputs, present NADPH-d staining in a sub-population of neurons that include all cell types. We have previously shown, by NADPH-diaphorase, that eye enucleation alters the intracellular distribution of NOS. Here, we studied the effect of cortical ablation on NOS expression by neurons in collicular superficial layers. Our results show that cortical ablation alters the proportion of different NOS-positive cell types, but not the intracellular distribution of the enzyme.O óxido nítrico apresenta diversos papéis biológicos e a óxido nítrico sintase (ONS) é expressa no sistema nervoso, co-localizando-se com a NADPH-diaforase. As camadas superficiais do colículo superior (CS), as quais recebem aferências retinianas e corticais, possuem marcação para NADPH-diaforase numa sub-população de neurônios que inclui todos os tipos celulares. Previamente demostramos, por NADPH-diaforase, que a enucleação ocular altera a distribuição intracelular da ONS. Neste trabalho estudamos o efeito da ablação cortical na expressão da ONS por neurônios das camadas superficiais coliculares. Nossos resultados demonstraram que a ablação cortical altera as proporções dos diferentes tipos celulares ONS positivos mas não a distribuição intracelular da ONS

Comparison among bone marrow mesenchymal stem and mononuclear cells to promote functional recovery after spinal cord injury in rabbits

<div><p>Abstract Purpose: To investigate the efficacy of allogeneic mesenchymal stem-cells and autologous mononuclear cells to promote sensorimotor recovery and tissue rescue. Methods: Female rabbits were submitted to the epidural balloon inflation method and the intravenous cells administrations were made after 8 hours or seven days after injury induction. Sensorimotor evaluation of the hindlimbs was performed, and the euthanasia was made thirty days after the treatment. Spinal cords were stained with hematoxylin and eosin. Results: Both therapies given 8 hours after the injury promoted the sensorimotor recovery after a week. Only the group treated after a week with mononuclear cells showed no significant recovery at post-injury day 14. In the days 21 and 28, all treatments promoted significant recovery. Histopathological analysis showed no difference among the experimental groups. Our results showed that both bone marrow-derived cell types promoted significant sensorimotor recovery after injury, and the treatment made at least a week after injury is efficient. Conclusion: The possibilities of therapy with bone marrow-derived cells are large, increasing the therapeutic arsenal for the treatment of spinal cord injury.</p></div