Abstract
BackgroundCerebral stroke occurs following ischemic and hemorrhagic lesions in the brain. Survival and recovery of stroke patients depend on the severity of the initial injury but also the therapeutic approaches applied for emergent lifesaving and continuing post-stroke management. Dl-3-n-Butylphthalide (NBP), an active compound derived from Chinese celery seeds, has shown clinical efficacy in the treatment of ischemic cerebral stroke.ResultsIn the present study we explored the therapeutic effect of NBP in a rat model of intracerebral hemorrhage (ICH), focusing on its potential role in promoting neovascularization in the perihemorrhagic zone. ICH was induced in male Sprague-Dawley rats by unilateral injection of autologous blood into the globus pallidus, with sham-operated (Sham group), vehicle-treated (ICH) and NBP-treated (at 10 and 25 mg/kg/Bid, p.o., ICH + NBP10 and ICH + NBP25, respectively) groups examined behaviorally, macroscopically, histologically and biochemically at 1, 3, 7 and 15 days (d) post operation. Rats in the ICH + NBP10 and ICH + NBP25 groups showed reduced Longa’s motor scores relative to the ICH groups at the 3 and 7d time points, while the hematoma volume was comparable in the two NBP relative to the ICH groups as measured at 7d and 15d. In the perihemorrhagic zone, the numeric density of blood vessels immunolabeled by CD34, an angiogenic marker, was greater in the ICH + NBP10 and ICH + NBP25 than ICH groups, more so in the higher dosage group, at 1, 3, 7 and 15d. Levels of the vascular endothelial growth factor (VEGF) and angiopoietins-2 (Ang-2) proteins were elevated in the NBP groups relative to the sham and vehicle controls in immunoblotting of tissue lysates from the injection region.ConclusionThese results suggest that NBP can alleviate neurological defects following experimentally induced local brain hemorrhage, which is associated with a potential role of this drug in promoting neovascularization surrounding the bleeding loci.
Highlights
Cerebral stroke occurs following ischemic and hemorrhagic lesions in the brain
The worst performance in the Intracerebral hemorrhage (ICH) groups occurred at the 3rd day post operation
The neurobehavioral deficit scores were significantly increased in the ICH groups in comparison with the Sham controls (P < 0.05 between all comparing pairs, ANOVA with Bonferroni’s post hoc test)
Summary
Cerebral stroke occurs following ischemic and hemorrhagic lesions in the brain. Tu et al BMC Neurosci (2020) 21:24 management and platelet transfusion, have significantly improved the outcome of cerebral stroke among patients [11,12,13,14,15,16]. Besides a space-occupying effect, the hematoma formed during ICH appears to rapidly impair regional blood flow, and causing an ischemic effect to the brain tissue adjacent to the bleeding site [17]. According to the concept of neurovascular unit (NVU) treatment in management of cerebral stroke, measures to promote angiogenesis are recommended to apply as early as possible when a stroke patient receives medical attention [18,19,20,21,22]. A better functioning microcirculation may play a crucial neuroprotective role, thereby improve the neurological recovery [23,24,25,26,27]
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