Contralateral hemisphere as a lifeguard which is supported by melatonin for molecular and functional recovery after stroke

Autor: Burcugul Altug-Tasa, Ahmet Burak Çağlayan, Bayram Yilmaz, Birsen Elibol, Ulkan Kilic, Omer Uysal, Ertugrul Kilic, Mustafa Çağlar Beker, Merve Beker
Rok vydání: 2020
Předmět:
DOI: 10.21203/rs.3.rs-45391/v1
Popis: Successful functional recovery from stroke is crucial in the rehabilitation of patients and mainly depends on several ischemia-induced processes, including cell survival and apoptosis. Melatonin is an interesting candidate for secondary stroke prevention due to its effect on signaling pathways. Therefore, we investigated the coordination of ipsilateral and contralateral hemispheres to evaluate delayed post-acute effect of melatonin on recovery of the cell survival and apoptosis after stroke. Melatonin was administered (4 mg/kg/day) intraperitoneally for 45 days, starting 3-day after 30-min of middle cerebral artery occlusion. The genes and proteins related to the cell survival and apoptosis were investigated by immunofluorescence, western blotting and RT-PCR techniques after behavioral experiments. Melatonin produced delayed neurological recovery by improving motor coordination, which was also reflected by enhanced neuronal survival and reduced apoptosis in the post-acute phase of stroke in both contralateral and ipsilateral hemispheres. The increase of NGF, Nrp1, c-jun; activation of AKT; and dephosphorylation of ERK and JNK at the 55th day showed that cell survival and apoptosis signaling molecules compete to contribute to the remodeling of brain. Furthermore, an increase in the CREB and Atf-1 expressions suggested the melatonin's strong reformative effect on neuronal regeneration. The contralateral hemisphere was more active at the latter stages of the molecular and functional regeneration which provides a further proof of principle about melatonin's action on the promotion of brain plasticity and recovery after stroke.
Databáze: OpenAIRE