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Inflammatory Cytokines are in Action: Brain Plasticity and Recovery after Brain Ischemia Due to Delayed Melatonin
Ulkan Kilic1, Birsen Elibol2, Merve Beker3
1Department of Medical Biology, Hamidiye School of Medicine, University of Health Sciences Turkey, Istanbul, Turkey.
Objectives:
Post-ischemic inflammation leads to apoptosis as an indirect cause of functional disabilities after the stroke. Melatonin may be a good candidate for the stroke recovery because of its anti-inflammatory effects. Therefore, we investigated the effect of melatonin on inflammation in the functional recovery of brain by evaluating ipsilesional and contralesional alterations.
Materials And Methods:
Melatonin (4 mg/kg/day) was intraperitoneally administered into the mice from the 3rd to the 55th day of the post-ischemia after 30 min of middle cerebral artery occlusion.
Results:
Melatonin produced a functional recovery by reducing the emigration of the circulatory leukocytes and the local microglial activation within the ischemic brain. Overall, the expression of the inflammation-related genes reduced upon melatonin treatment in the ischemic hemisphere. On the other hand, the expression level of the inflammatory cytokine genes raised in the contralateral hemisphere at the 55th day of the post-ischemia. Furthermore, melatonin triggers an increase in the iNOS expression and a decrease in the nNOS expression in the ipsilateral hemisphere at the earlier times in the post-ischemic recovery. At the 55th day of the post-ischemic recovery, melatonin administration enhanced the eNOS and nNOS protein expressions.
Conclusions:
The present molecular, biological, and histological data have revealed broad anti-inflammatory effects of melatonin in both hemispheres with distinct temporal and spatial patterns at different phases of post-stroke recovery. These outcomes also established that melatonin act recruitment of contralesional rather than of ipsilesional.
Insights
Melatonin administration promotes functional recovery after stroke by reducing inflammation in both brain hemispheres. This study highlights melatonin's potential for stroke recovery, impacting both ipsilesional and contralesional brain areas.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Post-ischemic inflammation contributes to apoptosis and functional deficits following stroke.
- Melatonin, known for its anti-inflammatory properties, is a potential therapeutic agent for stroke recovery.
Purpose of the Study:
- To investigate the effects of melatonin on brain inflammation and functional recovery after ischemic stroke.
- To evaluate melatonin's impact on both ipsilesional and contralesional brain alterations.
Main Methods:
- Mice were administered melatonin (4 mg/kg/day) intraperitoneally from day 3 to day 55 post-middle cerebral artery occlusion.
- Evaluated functional recovery, leukocyte emigration, microglial activation, and gene/protein expression of inflammatory markers.
Main Results:
- Melatonin treatment led to functional recovery by reducing leukocyte emigration and microglial activation in the ischemic brain.
- Melatonin decreased inflammation-related gene expression in the ischemic hemisphere but increased inflammatory cytokine genes in the contralateral hemisphere.
- Melatonin modulated iNOS, nNOS, and eNOS expression in a time- and hemisphere-dependent manner.
Conclusions:
- Melatonin exhibits broad anti-inflammatory effects in both brain hemispheres, with distinct temporal and spatial patterns during post-stroke recovery.
- Melatonin's therapeutic action involves the recruitment of cells to the contralesional hemisphere more than the ipsilesional hemisphere.
