Therapeutic potential of the novel hybrid molecule JM-20 against focal cortical ischemia in rats

• Published in: Journal of pharmacy & pharmacognosy research Vol. 4; no. 4; pp. 153 - 158
• Main Authors: Yanier Núñez Figueredo, Jeney Ramírez-Sanchez, Gisele Hansel, Gilberto L. Pardo-Andreu, Nelson Merino, Guillermo Aparicio, Rene Delgado-Hernández, Laura García-Pupo, Estael Ochoa-Rodríguez, Yamila Verdecia-Reyes, Diogo O. Souza
• Format: Journal Article
• Language: English
• Published: GarVal Editorial Ltda 01.07.2016
• Subjects: Cerebral ischemia; cylinder test; JM-20; neuroprotection; thermocoagulation
• ISSN: 0719-4250

Context: Despite the great mortality and morbidity of stroke, treatment options remain limited. We previously showed that JM-20, a novel synthetic molecule, possessed a strong neuroprotective effect in rats subjected to transient middle cerebral artery occlusion. However, to verify the robustness of the pre-clinical neuroprotective effects of JM-20 to get good prognosis in the translation to the clinic, it is necessary to use other experimental models of brain ischemia. Aims: To evaluate the neuroprotective effects of JM-20 following the onset of permanent focal cerebral ischemia induced in rats by thermocoagulation of blood into pial blood vessels of cerebral cortices. Methods: Ischemic lesion was induced by thermocoagulation of blood into pial blood vessels of primary motor and somatosensory cortices. Behavioral performance was evaluated by the cylinder testing for a period of 2, 3 and 7 days after surgery, and was followed by histopathological study in brain cortex stained with hematoxylin- eosin. Results: Ischemic injury resulted in impaired function of the forelimb evidenced by high asymmetry punctuation, and caused histopathological alterations indicative of tissue damage at cerebral cortex. JM-20 treatment (4 and 8 mg/kg) significantly decreased asymmetry scores and histological alterations with a marked preservation of cortical neurons. Conclusions: The effects of permanent brain ischemia were strongly attenuated by JM-20 administration, which expands and improves the current preclinical data of JM-20 as neuroprotector against cerebral ischemia, and strongly support the examination of its translation to the clinic to treat acute ischemic stroke.