Category Archives: Neuroprotection

C 024: Achyrocline satureioides (LAM) D.C. (MARCELA): PROTECTIVE EFFECTS IN PRIMARY NEURONAL CULTURES AND AGAINST AN ISCHEMIC INJURY IN VIVO

J Pharm Pharmacogn Res 2(Suppl. 1): S68, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 024: Achyrocline satureioides (LAM) D.C. (MARCELA): PROTECTIVE EFFECTS IN PRIMARY NEURONAL CULTURES AND AGAINST AN ISCHEMIC INJURY IN VIVO

Rivera F, Echeverry C, Arredondo F, Abin-Carriquiry JA, Martínez M, Dajas F.

Departamento de Neuroquímica. Instituto de Investigaciones Biológicas Clemente Estable. Unidad Asociada a Facultad de Ciencias. Universidad de la República. Avenida Italia 3318. Montevideo. Uruguay.
Abstract

Introduction: Achyrocline satureioides (AS) is a South American plant widely used in popular medicine. Experimental studies have confirmed its antioxidant and anti-inflammatory effects mainly due to its high content of polyphenols. In this work we evaluated the protective effects of an AS decoction (2%) in primary neuronal cultures against an oxidative injury and against an ischemic process in rats in vivo.

Methods: Dried flowers of AS were used for the preparation of the decoction. Primary cerebellar granule neurons in culture (DIV 7) were treated for 24h with AS decoction and subsequently exposed to an oxidative insult with H2O2 160 uM for 24h. MTT assay was used to analyze cell survival after the treatment. For in vivo assays, Sprague Dawley rats (250-350 g) were divided in 4 experimental groups (sham, ischemia, AS alone, and AS + ischemia) (n = 6/group). Animals were pre-treated with water or AS decoction for 7, 14 or 21 days followed by 24h of permanent middle cerebral artery occlusion. Consumption of food and AS decoction/water of the rats was evaluated daily and weight gain was monitored weekly. To assess functional deficits a behavioral test was performed, and cerebral damage was evidenced by TTC tetrazolium salt.

Results: AS (5 ug/mL total polyphenols) pre-treatment in neuronal cultures showed protective effects against H2O2 injury. AS pretreatment prevented the functional deficit caused by ischemic injury in all groups. Furthermore, AS pre-treatment for 21 days significantly decreased the infarction volume.

Conclusions: AS decoction (2%) pre-treatment showed protective effects against both oxidative injury in primary neuronal cultures, and in vivo ischemic brain injury. Its high polyphenolic content could explain such protective effects, mainly due to the antioxidant and antiinflammatory properties described for these compounds.

C 023: PRECLINICAL STUDIES OF A NEW HYBRID MOLECULE WITH NEUROPROTECTIVE EFFECTS IN THE TREATMENT OF CEREBRAL ISCHEMIA

J Pharm Pharmacogn Res 2(Suppl. 1): S67, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 023: PRECLINICAL STUDIES OF A NEW HYBRID MOLECULE WITH NEUROPROTECTIVE EFFECTS IN THE TREATMENT OF CEREBRAL ISCHEMIA

Nuñez Y1, Pardo G2, Ramírez J1, García L1, Delgado R1, Merino N1, Valdés O1, Ochoa E2, Verdecia Y2, Iglesias L1, Onofre D3, Salbego C3, Hansel G3, Nicoloso E3, Porto M1.

1Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba, E-mail: yaniernf@infomed.sld.cu
2Centro de Estudio para las Investigaciones y Evaluaciones Biológicas, Instituto de Farmacia y Alimentos, Universidad de La Habana, ave. 23 # 21425 e/214 y 222, La Coronela, La Lisa, CP 13600, La Habana, Cuba.
3Laboratorio de Síntesis Orgánica de La Facultad de Química de La Universidad de La Habana (Zapata s/n entre G y Carlitos Aguirre, Vedado Plaza de la Revolución, CP 10400, La Habana, Cuba.
4Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo, Porto Alegre, RS 90035-003, Brazil.
Abstract

Introduction: Cerebral ischemia has a high incidence at present, their frequency increases with increasing life expectancy and the drugs available have low effectiveness. Clinical evidence has shown therapeutic failure of neuroprotective drugs, often caused by the use of drugs that act on a single mediator of damage in a disease that involves a complex variety of events. That is why the study of multiligands compounds that may affect several steps of the ischemic cascade, could be an attractive therapeutic option for this disease.

Material and methods: In the present work we evaluated, a novel 1,5benzodiazepines with the presence of a 1,4 dihydropyridine moiety fused to the benzodiazepine ring (JM-20) in different experimental models associated with ischemic brain damage, including behavioral models to evaluate GABAergic activity, cellular models for evaluate cytotoxicity induced by glutamate, hydrogen peroxide and oxygen glucose deprivation. Also we evaluated the effect of JM-20 on different parameters associated with mitochondrial dysfunction and on histological, behavioral and biochemical alterations in animal models of stroke.

Results: The main results obtained show that JM-20 has a neurosedative profile similar to diazepam, however the presence of the dihydropyridine moiety in their structure, could be inhibiting damage associated exacerbated calcium in flux. Moreover, JM-20 showed strong neuroprotective effect in animals and cell models associated with the cerebral ischemia and on different parameters of mitocondrial dysfunction responsible of the neuronal death.

C 022: THE GUANINE-BASED PURINERGIC SYSTEM AS A NEW TARGET FOR NEUROPROTECTION AGAINST GLUTAMATERGIC EXCYTOTOXICITY

J Pharm Pharmacogn Res 2(Suppl. 1): S65, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 022: THE GUANINE-BASED PURINERGIC SYSTEM AS A NEW TARGET FOR NEUROPROTECTION AGAINST GLUTAMATERGIC EXCYTOTOXICITY

Souza DO.

Departamento de Bioquímica, PPG em Bioquímica e PPG em Educação em Ciências, ICBS, UFRGS. Rua Ramiro Barcelos, 2600 – Anexo. CEP: 90035-003, Porto alegre, RS, Brazil.
Abstract

Glutamate is the main excitatory neurotransmitter in mammalian CNS, essential for brain activities, as those involved in development, ageing, memory, and adaptation to the environment. However, hyper activation of the glutamatergic system may be potentially neurotoxic, involved in the pathogenesis of various acute and chronic brain injuries. The main process responsible by maintaining the extracellular glutamate levels below toxic levels, thus favoring the physiological glutamatergic tonus, is the glutamate uptake exerted by transporters located in neural cell membranes, mainly in astrocytes. Our group has given strong evidence that the guanine-based purinergic system is effectively neuroprotective against glutamate toxicity, in acute and chronic animal models, both in vitro and in vivo studies. Our results indicate that nucleoside guanosine (Guo) exerts neuroprotection. In vivo Guo i.c.v., i.p. or orally administered in rodents protects against brain injury caused by overstimulation of the glutamatergic system. In vitro studies, Guo protects cell death in brain slices caused by in vitro ischemia. Searching for mechanisms implicated in this neuroprotection, we demonstrated that: i) Guo stimulates the astrocytic glutamate uptake (in astrocyte cultures and brain slices), the main process involved in endogenous neuronal protection; ii) brain induced-injuries decrease glutamate uptake by brain slices and this decrease is reversed by Guo only when it acts as anticonvulsant; iii) brain oxidative stress caused by glutamate toxicity in experimental brain injury models is reversed by Guo administration. Thus we propose that the stimulatory effect on glutamate uptake and/or its antioxidant activity are involved in the neuroprotective actions of Guo. These results encourage further studies aiming at the therapeutic use in humans of Guo in acute (hypoxia, ischemia, brain traumatism) and chronic (neurodegenerative diseases) brain injuries involving glutamate excytotoxicity.