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.
Highlights
Stroke is a leading cause of adult long-term disability, mortality, and morbidity worldwide.Currently, thrombolytic therapy with tissue plasminogen activator still remains the first option for the treatment of ischemic stroke, only a small population of patients have seen any clinical benefits due to its narrow therapeutic window after stroke onset [1]
To investigate the neuroprotective potential against cerebral ischemia brain injury, propranolol was delivered into rats 30 min prior to ischemia
Our groups have described a state of hyperglycemia and insulin resistance, along with elevated circulating levels of adrenaline and noradrenaline, in rat models of cerebral ischemia
Summary
Stroke is a leading cause of adult long-term disability, mortality, and morbidity worldwide.Currently, thrombolytic therapy with tissue plasminogen activator (tPA) still remains the first option for the treatment of ischemic stroke, only a small population of patients have seen any clinical benefits due to its narrow therapeutic window after stroke onset [1]. Clinical findings indicate that hyperglycemia is critical in counterbalancing the therapeutic benefits and increasing the adverse complications of tPA through an action mode related to inflammation exacerbation [2,3,4,5] Despite their protective and regenerative potential, overwhelming hyperglycemia and neuroinflammation have been implicated in the pathogenesis of stroke. Rodent studies have revealed the crosstalk among tPA, hyperglycemia, and neuroinflammation in cerebral ischemic brain injury, and the existing therapeutic benefits by means of targeting hyperglycemia and neuroinflammation [6,7,8,9,10] These phenomena underscore the importance of exploring the underlying mechanisms of stroke-accompanied hyperglycemia and neuroinflammation, as well as highlighting their therapeutic potential towards combating stroke disease and related complications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
