Abstract
BackgroundDespite the recent advances in the acute stroke care, treatment options for long-term disability are limited. RPh201 is a botany-derived bioactive compound that has been shown to exert beneficial effects in various experimental models of neural injury. The present study evaluated the effect of delayed RPh201 treatment on long term functional recovery after stroke.MethodsAdult male Wistar rats subjected to embolic middle cerebral artery occlusion (MCAO) were randomized into the following experimental groups (n = 20/group): (1) RPh201 treatment, and (2) Vehicle (cottonseed oil). RPh201 (20 μl) or Vehicle were subcutaneously administered twice a week for 16 consecutive weeks starting at 21 days after MCAO. An array of behavioral tests was performed up to120 days after MCAO.ResultsIschemic rats treated with RPh201 exhibited significant (p < 0.05) improvement of neurological function measured by adhesive removal test, foot-fault test, and modified neurological severity score at 90 and 120 days after MCAO. Immunohistochemistry analysis showed that RPh201 treatment robustly increased neurofilament heavy chain positive axons and myelin basic protein densities in the peri-infarct area by 61% and 31%, respectively, when compared to the Vehicle treatment, which were further confirmed by Western blot analysis. The RPh201 treatment did not reduce infarct volume.ConclusionOur data demonstrated that RPh201 has a therapeutic effect on improvement of functional recovery in male ischemic rats even when the treatment was initiated 21 days post stroke. Enhanced axonal and myelination densities by RPh201 in ischemic brain may contribute to improved stroke recovery.
Highlights
Stroke is a leading cause of disability worldwide (Lozano et al, 2012; Murray et al, 2012)
As a substantial proportion of stroke survivors suffer from longterm disability that imposes an enormous medical and societal burden (Wolfe, 2000; Feigin et al, 2014), development of effective treatments to improve neurological function for stroke patients are of major importance
A recent Phase 2 clinical trial shows that long-term RPh201 treatment improves visual function in patients with previous non-arteritic anterior ischemic optic neuropathy (NAION), which highlights the therapeutic potential of RPh201 for central nervous system (CNS) diseases (Rath et al, 2019)
Summary
Stroke is a leading cause of disability worldwide (Lozano et al, 2012; Murray et al, 2012). RPh201, an extract of gum mastic, is being developed by Regenera Pharma for the treatment of various neurological diseases. Clinical evaluations on the safety and therapeutic effects of RPh201 for patients with central nervous system (CNS) diseases are underway (Cummings et al, 2019; Rath et al, 2019). A recent Phase 2 clinical trial shows that long-term RPh201 treatment improves visual function in patients with previous NAION, which highlights the therapeutic potential of RPh201 for CNS diseases (Rath et al, 2019). The present study was under taken to investigate whether post stroke RPh201 treatment improves neurological functional recovery in rats after embolic stroke. The present study evaluated the effect of delayed RPh201 treatment on long term functional recovery after stroke
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