Progesterone inhibits inflammatory response pathways after permanent middle cerebral artery occlusion in rats

AbstractIschemic stroke is one of the major causes of death and permanent disability in the world. However, the molecular mechanisms surrounding tissue damage are complex and further studies are needed to gain insights necessary for development of treatment. Prophylactic treatment by administration of cytosine-guanine (CpG) oligodeoxynucleotides has been shown to provide neuroprotection against anticipated ischemic injury. CpG binds to Toll-like receptor 9 (TLR9) causing initialization of an inflammatory response that limits visible ischemic damages upon subsequent stroke. Here, we use nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging (MSI) to characterize molecular effects of CpG preconditioning prior to middle cerebral artery occlusion (MCAO) and reperfusion. By doping the nano-DESI solvent with appropriate internal standards, we can study and compare distributions of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in the ischemic hemisphere of the brain despite the large changes in alkali metal abundances. Our results show that CpG preconditioning not only reduces the infarct size but it also decreases the degradation of PC and accumulation of LPC species, which indicates reduced cell membrane breakdown and overall ischemic damage. Our findings show that molecular mechanisms of PC degradation are intact despite CpG preconditioning but that these are limited due to the initialized inflammatory response.

Download Full-text

Decreased focal inflammatory response by G-CSF may improve stroke outcome after transient middle cerebral artery occlusion in rats

Journal of Neuroscience Research ◽

10.1002/jnr.21341 ◽

2007 ◽

Vol 85 (10) ◽

pp. 2167-2174 ◽

Cited By ~ 36

Author(s):

Yoshihide Sehara ◽

Takeshi Hayashi ◽

Kentaro Deguchi ◽

Hanzhe Zhang ◽

Atsushi Tsuchiya ◽

...

Keyword(s):

Inflammatory Response ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Artery Occlusion ◽

Stroke Outcome ◽

Cerebral Artery Occlusion

Download Full-text

Apocynin promotes neural function recovery and suppresses neuronal apoptosis by inhibiting Tlr4/NF-κB signaling pathway in a rat model of cerebral infarction

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738418817700 ◽

2018 ◽

Vol 32 ◽

pp. 205873841881770

Author(s):

Lemen Pan ◽

Shuxia Qian

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Cerebral Infarction ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Neuronal Apoptosis ◽

Artery Occlusion ◽

Cerebral Artery Occlusion ◽

And Oxidative Stress

Occlusion of arteries in the brain is a common cause of cerebral infarction which induces inflammatory response and oxidative stress resulting in neuronal apoptosis and disruption of neurological function. The present study investigated the protective roles of an nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin, against cerebral infarction. Rat went through a surgery of middle cerebral artery occlusion and a subset of rats was treated with apocynin by intraperitoneal injection. The volume of cerebral infarction and water content were measured. Neuronal apoptosis, inflammatory response, and oxidative stress were assessed following middle cerebral artery occlusion and apocynin treatment. We found that apocynin significantly improved neurological function, increased forelimb placement test scores, and suppressed balance beam walk latency in rats with cerebral infarction. Histological and biochemistry analysis revealed that apocynin lead to a significant reduction in the volume of cerebral infarction as well as cerebral water content, suppressed neuronal apoptosis, oxidative stress, and inflammatory response induced by middle cerebral artery occlusion. Finally, we found that apocynin suppressed Tlr4/nuclear factor-k-gene binding signaling pathway that was upregulated in rats with cerebral infarction. Our results indicate that apocynin may represent a potent therapeutic strategy in alleviating neurological dysfunctions in patients with cerebral infarction.

Download Full-text