Hypothermia treatment ameliorated cyclin-dependent kinase 5-mediated inflammation in ischemic stroke and improved outcomes in ischemic stroke patients

Abstract

OBJECTIVES:The inflammatory response is a key mechanism of neuronal damage and loss during acute ischemic stroke. Hypothermia has shown promise as a treatment for ischemic stroke. In this study, we investigated the molecular signaling pathways in ischemic stroke after hypothermia treatment.METHODS:Cyclin-dependent kinase 5 (CDK5) was overexpressed or silenced in cultured cells. Nuclear transcription factor-κB (NF-κB) activity was assessed by measurement of the luciferase reporter gene. An ischemic stroke model was established in Sprague-Dawley (SD) rats using the suture-occluded method. Animals were assigned to three groups: sham operation control, ischemic stroke, and ischemic stroke + hypothermia treatment groups. Interleukin 1β (IL-1β) levels in the culture supernatant and blood samples were assessed by ELISA. Protein expression was measured by Western blotting.RESULTS:In HEK293 cells and primary cortical neuronal cultures exposed to hypothermia, CDK5 overexpression was associated with increased IL-1β, caspase 1, and NF-κB levels. In both a murine model of stroke and in patients, increased IL-1β levels were observed after stroke, and hypothermia treatment was associated with lower IL-1β levels. Furthermore, hypothermia-treated patients showed significant improvement in neurophysiological functional outcome.CONCLUSIONS:Overall, hypothermia offers clinical benefit, most likely through its effects on the inflammatory response.

Hypothermia treatment reduced cyclin-dependent kinase 5-mediated inflammation in ischemic stroke and improved outcomes in ischemic stroke patients

“…We read with interest the article by Sun et al concerning the reduction of inflammation with therapeutic hypothermia in acute ischemic stroke (1). In this study, the authors demonstrated the improvement of inflammatory biomarkers after hypothermia treatment in both animal cerebral infarct models and patients with ischemic stroke.…”

Micro RNAs and Circular RNAs in Different Forms of Otitis Media

“…A study by Sui et al confirmed the negative correlation between miR-142-5p and cyclin-dependent kinase 5 (CDK5) in terms of expression and regulation [ 32 ]. CDK5 was previously reported to contribute to increasing inflammatory responses [ 69 , 70 ]. Sui et al observed CDK5 overexpression in cholesteatoma tissue samples, which was found to be positively correlated with levels of the cytokines TNF-α, TGF-β1, IL-5, IL-6, and IL-17A [ 32 ].…”

The role of Cdk5 in neurological disorders

“…Cerebral ischemia is one of the most serious public health problems worldwide (Tolonen et al, 2005 ). The important pathophysiological mechanisms of ischemic stroke are neuroinflammation, oxidative stress, calcium overload, mitochondrial fragmentation, and Golgi stress caused by ischemia and hypoxia (Sun et al, 2019 ). As a unique Cdk in the nervous system, Cdk5 has been demonstrated to play an important role in the pathological process of ischemic stroke.…”