RESUMO
Neuroprotection against excitotoxicity by a combined therapy with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the L-type Ca2+ channel blocker nimodipine was examined using an in vivo rat model of NMDA-induced neurodegeneration. Attention was focused on the neuroprotective potential of this combined drug treatment before and after NMDA-exposure. NMDA was unilaterally injected in the magnocellular nucleus basalis (MBN). Neuronal damage was assessed 12 days after the NMDA-injection by measuring the reduction of cholinergic cortical fibres that originate from the MBN neurons. In controls that received no drug treatment, NMDA-exposure damaged MBN neurons such that 66% of the cholinergic terminals were lost in the ipsilateral parietal cortex. Pretreatment with a nimodipine diet (860 ppm) combined with application of MK-801 (5 mg/kg i.p.) before NMDA-exposure reduced fibre loss by 89% thereby providing a near complete neuroprotection. Combined therapy of MK-801 (5 mg/kg i.p.) and nimodipine (15 mg/kg i.p.) 8 min after NMDA-infusion reduced neuronal injury by 82%, while the same combination given 2 h after the excitotoxic treatment still yielded a 66% protection against neurotoxic damage invoked by NMDA. In conclusion, the present data show that a dual blockade of NMDA-channels and voltage-dependent calcium channels (VDCC's) up to 2 h after NMDA-exposure is able to provide a significant protection against NMDA-neurotoxicity.
Assuntos
Envelhecimento/fisiologia , Encéfalo/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , N-Metilaspartato/toxicidade , Degeneração Neural/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Nimodipina/farmacologia , Análise de Variância , Animais , Encéfalo/patologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Masculino , N-Metilaspartato/antagonistas & inibidores , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/patologia , Neurônios/patologia , Ratos , Ratos WistarRESUMO
The effect of the chronic oral application of NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide (NO) production, was studied on hypothalamic blood flow (HBF) and hypothalamic nitric oxide synthase (NOS) activity in rats. L-NAME was dissolved in the drinking water, in a concentration of 0.1 mg/ml, and was administered for 1 week. In the chronic L-NAME pretreated animals significantly reduced hypothalamic NOS activity and marked hypothalamic vasoconstriction were observed, the latter of which was counteracted by sustained systemic arterial hypertension, while HBF remained unchanged. The present model of chronic NOS blockade may be useful to assess the physiological functions of NO in the regulation of cerebral blood flow in the normally perfused brain.
Assuntos
Arginina/análogos & derivados , Inibidores Enzimáticos/farmacologia , Hipotálamo/irrigação sanguínea , Hipotálamo/enzimologia , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Arginina/farmacologia , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Cálcio/fisiologia , Circulação Cerebrovascular/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Masculino , NG-Nitroarginina Metil Éster , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/efeitos dos fármacos , Mecânica Respiratória/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacosAssuntos
Regulação Enzimológica da Expressão Gênica , Glutationa Peroxidase/biossíntese , Hipóxia Encefálica/enzimologia , Ataque Isquêmico Transitório/enzimologia , Prosencéfalo/enzimologia , Animais , Autorradiografia , Corpo Estriado/enzimologia , Expressão Gênica , Hipocampo/enzimologia , Hibridização In Situ , Masculino , Especificidade de Órgãos , Células Piramidais/enzimologia , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Radioisótopos de EnxofreRESUMO
Long chain cyclopropane fatty acids were observed in the sulfolipid fraction extracted from leaves of the early spring plants Galanthus nivalis L. and Anthriscus silvestris L. (Hoffm.). The content of cyclopropane fatty acids with 25 carbon atoms appeared to be clearly correlated with earliness in spring, and it ranged from 68% (G. nivalis L., snow drop) to 0.5% (wheat). Several long chain cyclopropane fatty acids were found in the drought-tolerant Corynephorus canescens (L.) P.B., exclusively in the phosphatidyl choline fraction.