Abstract
BackgroundIschemic stroke is the third leading cause of death in adults worldwide and is the first leading cause of long-term disability. Neurogenesis plays an important role in promoting behavioral recovery after stroke. Huatuo Zaizao pill (HT), a traditional Chinese medicine, has been used clinically in China to promote the rehabilitation after stroke, but the underlying mechanism of action was still unclear. This study is to investigate the effects of HT on the functional recovery in a rat model of cerebral ischemia-reperfusion (I/R) injury, and the potential molecular mechanisms.MethodsRats were randomly divided into sham, model with cerebral I/R injury, or HT-treated groups, then administered orally with vehicle (for the sham and model group) or HT (0.5, 1.0, or 2.0 mg/kg) respectively, for 3 or 7 days. Functional recovery was assessed by cylinder test, beam walking test, and adhesive test. Neurogenesis was investigated by double immunofluorescence staining for 5-ethynyl-2-deoxyuridine (EdU) and neuronal nuclear protein (NeuN). The proteins of kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were assayed by western blotting. The level of BDNF mRNA was evaluated by RT-PCR.ResultsCompared with the model group, treatment with HT significantly promoted functional recovery in I/R injured rats (p < 0.05 or p < 0.01). The generation of new neurons was increased in the HT groups. HT treatment for 3 days increased the level of BDNF mRNA in I/R injured rats. Expression of PKA, phosphorylated CREB, and BDNF were significantly (p < 0.05) increased with the 7-day HT treatment.ConclusionsThese results indicated that HT treatment could promote functional recovery after stroke. HT enhanced the expression of BDNF and increased the level of neurogenesis in cerebral I/R animal, which might be associated with the functional recovery.
Highlights
Ischemic stroke is the third leading cause of death in adults worldwide and is the first leading cause of long-term disability
The cAMP/proteins of kinase A (PKA)/CREB signal transduction pathway plays a pivotal role in multiple aspects of neurogenesis [4]
I/R injury led to a motor deficit in the impaired forepaw, which was indicated by a significant preference for the use of the unimpaired forepaw compared with sham group (p < 0.01)
Summary
Ischemic stroke is the third leading cause of death in adults worldwide and is the first leading cause of long-term disability. Neurogenesis plays an important role in promoting behavioral recovery after stroke. The process of neurogenesis involves cell proliferation, migration, and differentiation in the ischemic region of brain [2], and is regulated by a series of signaling pathways. Duan et al BMC Complementary and Alternative Medicine (2017) 17:19 binding protein (CREB) is associated with neuronal development, synaptic plasticity, and regeneration and cell survival in response to cerebral ischemia [3]. The cAMP/PKA/CREB signal transduction pathway plays a pivotal role in multiple aspects of neurogenesis [4]. Brain-derived neurotrophic factor (BDNF) regulates multiple steps of neurogenesis, including proliferation, migration, differentiation, and survival [5]
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