Effects of β-Adrenergic Blockade on Metabolic and Inflammatory Responses in a Rat Model of Ischemic Stroke

Abstract

Ischemic stroke provokes an inflammatory response concurrent with both sympathetic nervous system activation and hyperglycemia. Currently, their crosstalk and consequences in stroke outcomes are of clinical attraction. We have provided experimental evidence showing the suppressive effects of the nonselective β-adrenoreceptor antagonist propranolol on hyperglycemia, inflammation, and brain injury in a rat model experiencing cerebral ischemia. Pretreatment with propranolol protected against postischemic brain infarction, edema, and apoptosis. The neuroprotection caused by propranolol was accompanied by a reduction in fasting glucose, fasting insulin, glucose tolerance impairment, plasma C-reactive protein, plasma free fatty acids, plasma corticosterone, brain oxidative stress, and brain inflammation. Pretreatment with insulin alleviated—while glucose augmented—postischemic brain injury and inflammation. Additionally, the impairment of insulin signaling in the gastrocnemius muscles was noted in rats with cerebral ischemia, with propranolol improving the impairment by reducing oxidative stress and tumor necrosis factor-α signaling. The anti-inflammatory effects of propranolol were further demonstrated in isoproterenol-stimulated BV2 and RAW264.7 cells through its ability to decrease cytokine production. Despite their potential benefits, stroke-associated hyperglycemia and inflammation are commonly linked with harmful consequences. Our findings provide new insight into the anti-inflammatory, neuroprotective, and hypoglycemic mechanisms of propranolol in combating neurodegenerative diseases, such as stroke.

Inhibition of Long Noncoding RNA SNHG15 Ameliorates Hypoxia/Ischemia-Induced Neuronal Damage by Regulating miR-302a-3p/STAT1/NF-κB Axis

“…Oxidative stress and excessive activation of inflammation are typical causative factors of acute IS. 30 Oxidative stress is mediated by reactive oxygen species (ROS) produced by the body. The imbalance between oxidation and antioxidant substances causes oxidative damage to tissues and cells.…”

Neuroinflammation-Associated Alterations of the Brain as Potential Neural Biomarkers in Anxiety Disorders

“…Lin et al provided experimental evidence showing the suppressive effects of propranolol on inflammation and brain injury. Pretreatment with propranolol was shown to protect against postischemic brain infarction, edema, and apoptosis; the neuroprotection caused by propranolol was accompanied by a reduction in plasma c-reactive protein, plasma free fatty acids, plasma corticosterone, brain oxidative stress, and brain inflammation [ 182 ]. Further systematic research on the effects of propranolol treatment for anxiety disorders, and the possible mechanisms of such treatment effects, i.e., attenuation of neuroinflammation and consequent neurotoxic effects, should be conducted.…”

Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization

“…We cannot, however, exclude the possibility that present observations are a consequence of developmental adaptations in mice with constitutive IP 3 R2 deletion. Interestingly, recent studies have shown that treatment with the beta-AdR blocker propranolol reduces ischemic stroke damage in mice, suggesting a significant role of beta AdRs in the normalization of extracellular ion balance 18 , 61 . Further study is warranted to characterize the efficacy of individual AdR blockers as well as their synergy and optimal dosages.…”