Neuropsychiatric Disease and Treatment (Dec 2020)
A Novel Cerebroprotein Hydrolysate, CH1, Ameliorates Chronic Focal Cerebral Ischemia Injury by Promoting White Matter Integrity via the Shh/Ptch-1/Gli-1 Signaling Pathway
Abstract
Wen Cao,1 Cong Zhang,1 Rong Chen,2,3 Qianqian Wu,1 Renhao Xu,2,3 Lan Zhang,1 Xiangjian Zhang1– 3 1Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People’s Republic of China; 2Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang, Hebei 050000, People’s Republic of China; 3Hebei Vascular Homeostasis Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, People’s Republic of ChinaCorrespondence: Xiangjian ZhangDepartment of Neurology, Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, People’s Republic of ChinaTel +86 15803210578Fax +86 31166002822Email [email protected]: Strokes are devastating as there are no current therapies to prevent long-term neurological deficits. Previous studies reported that cerebroprotein hydrolysate (CH) plays a role in neuronal protection in acute phase after ischemic stroke, while the long-term effects of CH upon brain plasticity and neurological outcomes after stroke are still uncertain. To address these gaps, we assessed the effect of a new cerebroprotein hydrolysate, CH1, on long-term gray and white matter integrity as well as axonal plasticity in the late phase after ischemic stroke and the potential mechanisms.Methods: Adult male mice were subjected to permanent distal middle cerebral artery occlusion (dMCAO), followed by daily intraperitoneal injection of CH1 for 14 days. Motor function was measured weekly through behavioral neurological evaluations. Gray matter intensity and white matter intensity were examined by immunofluorescence staining. The sonic hedgehog (Shh) inhibitor cyclopamine (CYC) was injected to determine the involvement of the Shh pathway in the therapeutic effects of CH1.Results: We found that intraperitoneal delivery of CH1, compared to vehicle administration, significantly improved long-term neurological outcomes at various times and promoted neuronal viability at 14 days but not at 28 days after stroke. Importantly, CH1 mitigated stroke-induced white matter injury and facilitated axonal plasticity in the late stage after stroke.Conclusion: These results unveil a previously unappreciated role for CH in the repair of white matter and brain plasticity after stroke.Keywords: ischemic stroke, cerebroprotein hydrolysate, axonal plasticity, white matter integrity, Shh pathway
