RESUMEN
The neuroprotective effect of epidermal growth factor (EGF) has been documented in different contexts, but its potential benefits in peripheral neuropathies have been little studied. We investigated the neuroprotective action of EGF in experimental neuropathy induced by acrylamide (ACR). Mice and rats were treated chronically with acrylamide for 6 and 8 weeks, respectively. Concurrently they received EGF in daily doses of 1 and 5 mg/kg in mice and 3 mg/kg in rats, or saline (PBS). ACR severely affected the neurological score, the muscle strength, and the muscle potential M, in mice, as well as F-waves (F-Wii), sensory potentials (SPii), and apomorphine-induced penile erection, in rats. EGF reduced the ACR effects in both species. A dose-dependent effect of EGF was manifested in the proportion of diseased animals at the end of treatments, as well as in the reduction of M amplitude throughout the treatment. F-Wii parameters were less protected by EGF than SP. The results show a protective effect of EGF in acrylamide-induced neuropathy and support previous studies concerning the neuroprotective action of this peptide.
Asunto(s)
Acrilamida/toxicidad , Factor de Crecimiento Epidérmico/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Potenciales de Acción/fisiología , Animales , Apomorfina/farmacología , Modelos Animales de Enfermedad , Agonistas de Dopamina/farmacología , Estimulación Eléctrica , Factor de Crecimiento Epidérmico/química , Fuerza de la Mano/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Examen Neurológico , Fármacos Neuroprotectores/química , Erección Peniana/efectos de los fármacos , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
BACKGROUND: Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP-6) in stroke models has accumulated evidence of neuroprotective effects from several studies, but needs further support before clinical translation. Comparing EGF + GHRP-6 to hypothermia, a gold neuroprotection standard, may contribute to this purpose. OBJECTIVES: The aims of this study were to compare the neuroprotective effects of a combined therapy based on EGF + GHRP-6 with hypothermia in animal models of (a) global ischemia representing myocardial infarction and (b) focal brain ischemia representing ischemic stroke. METHODS: (a) Global ischemia was induced in Mongolian gerbils by a 15-min occlusion of both carotid arteries, followed by reperfusion. (b) Focal brain ischemia was achieved by intracerebral injection of endothelin 1 in Wistar rats. In each experiment, three ischemic treatment groups - vehicle, EGF + GHRP-6, and hypothermia - were compared to each other and to a sham-operated control group. End points were survival, neurological scores, and infarct volume. RESULTS: (a) In global ischemia, neurological score at 48-72 h, infarct volume, and neuronal density of hippocampal CA1 zone in gerbils treated with EGF + GHRP-6 were similar to the hypothermia-treated group. (b) In focal ischemia, the neurologic score and infarct volume of rats receiving EGF + GHRP-6 were also similar to animals in the hypothermia group. DISCUSSION: With hypothermia being a good standard neuroprotectant reference, these results provide additional proof of principle for EGF and GHRP-6 co-administration as a potentially neuroprotective stroke therapy.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/uso terapéutico , Hipotermia Inducida/métodos , Fármacos Neuroprotectores/uso terapéutico , Oligopéptidos/uso terapéutico , Accidente Cerebrovascular/terapia , Análisis de Varianza , Animales , Temperatura Corporal/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Modelos Animales de Enfermedad , Quimioterapia Combinada , Gerbillinae , Masculino , Examen Neurológico , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
A previously unknown disease, termed epidemic neuropathy (EN), occurred in Cuba between 1991 and 1993. When samples of cerebrospinal fluid (CSF) from 45 patients with EN and 11 controls were inoculated into cultures of VERO cells, almost all (93%) of the samples from the cases of EN but only one (9%) of the control samples produced a slowly progressing cytopathological effect (CPE). Although the results of other studies indicated the presence of a picornavirus-like virus in CSF samples from EN cases, the CPE and other physico-chemical characteristics observed were not those expected of picorn-viruses. Several aetiological factors may have contributed to EN but at least one virus could have played a major role.
Asunto(s)
Brotes de Enfermedades , Enfermedades del Nervio Óptico/virología , Enfermedades del Sistema Nervioso Periférico/virología , Adulto , Animales , Chlorocebus aethiops , Cuba/epidemiología , Humanos , Persona de Mediana Edad , Enfermedades del Nervio Óptico/líquido cefalorraquídeo , Enfermedades del Nervio Óptico/epidemiología , Enfermedades del Sistema Nervioso Periférico/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Periférico/epidemiología , Células VeroRESUMEN
Transgenic mice and rabbits were generated using a chimeric gene comprising the human erythropoietin (hEPO) cDNA under the 5' and 3' regulatory sequences of the rabbit whey acidic protein gene. Transgenic mice expressed hEPO at levels of 0.01 mg/l in the milk of lactating females showing that the genetic construct was functional. Reverse transcriptase polymerase chain reaction with RNA from various tissues showed that this transgene was expressed mainly in the ovary and mammary gland. In rabbits, we demonstrated the germ line transmission of the transgene. The hEPO was obtained in the milk of lactating females at levels of up to 0.0003 mg/l. Although the expression levels were low, biologically active hEPO was obtained in the milk of transgenic rabbits without any apparent detrimental effect for the animals. In vitro, the specific activity of the rabbit-derived hEPO was higher than that reported for the natural hEPO, thus suggesting differences in the glycosylation pattern in at least part of the molecules secreted by the mammary gland of transgenic rabbits.
Asunto(s)
Animales Modificados Genéticamente/genética , Eritropoyetina/biosíntesis , Lactancia/genética , Glándulas Mamarias Animales/metabolismo , Ratones Transgénicos/genética , Animales , ADN Complementario/genética , Femenino , Ratones , ConejosRESUMEN
Transgenic mice and rabbits were generated using a chimeric gene comprising the human erythropoietin (hEPO) cDNA under the 5' and 3' regulatory sequences of the rabbit whey acidic protein gene. Transgenic mice expressed hEPO at levels of 0.01 mg/l in the milk of lactating females showing that the genetic construct was functional. Reverse transcriptase polymerase chain reaction with RNA from various tissues showed that this transgene was expressed mainly in the ovary and mammary gland. In rabbits, we demonstrated the germ line transmission of the transgene. The hEPO was obtained in the milk of lactating females at levels of up to 0.0003 mg/l. Although the expression levels were low, biologically active hEPO was obtained in the milk of transgenic rabbits without any apparent detrimental effect for the animals. In vitro, the specific activity of the rabbit-derived hEPO was higher than that reported for the natural hEPO, thus suggesting differences in the glycosylation pattern in at least part of the molecules secreted by the mammary gland of transgenic rabbits