ReferenceID 1738

l-Borneol and d-Borneol promote transdifferentiation of astrocytes into neurons in rats by regulating Wnt/Notch pathway to exert neuroprotective effect during recovery from cerebral ischaemia

Phytomedicine

Background: The Chinese medicines Borneolum and l-Borneolum have neuroprotective effects on acute cerebral ischaemia-reperfusion (IR) in rats. Research on their effects during recovery from cerebral IR is lacking. Cerebr

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Reference Id
1738
Evidence Id
18328
Core Evidence Id
18328
Source Reference Id
3456
Herb2 Reference Id
HBREF004253
Subject Paper Key
HBIN022813_36610167
Pubmed Id
36610167
Doi
10.1016/j.phymed.2022.154583
Paper Title
l-Borneol and d-Borneol promote transdifferentiation of astrocytes into neurons in rats by regulating Wnt/Notch pathway to exert neuroprotective effect during recovery from cerebral ischaemia
Paper Abstract
Background: The Chinese medicines Borneolum and l-Borneolum have neuroprotective effects on acute cerebral ischaemia-reperfusion (IR) in rats. Research on their effects during recovery from cerebral IR is lacking. Cerebral ischaemia can activate astrocytes for conversion into neurons. Neurogenesis cannot be achieved without nutritional support from an improved brain microenvironment through the blood circulation. Purpose: The purpose of this study was to determine whether Borneolum and l-Borneolum can promote transdifferentiation of astrocytes into neurons by regulating the Wnt/Notch pathway to exert neuroprotective effects during recovery from cerebral ischaemia. Study design and methods: A suture crossing the external carotid artery to occlude the middle cerebral artery was used to prepare a model of cerebral IR (Longa et al., 1989). The Longa neurological function score, modified neurological severity score, tape removal test and grid misstep experiment were used to evaluate motor nerve function. Triphenyltetrazolium chloride was used to determine the extent of cerebral infarction. Left/right hemisphere contrast was used to measure brain atrophy. Astrocytes labelled with adeno-associated virus were used to track their fate after transdifferentiation. Laser speckle contrast imaging was used to observe the effects of l-Borneolum and Borneolum on cerebral blood flow. Immunofluorescence and western blotting were used to investigate their mechanisms. Results: l-Borneolum and Borneolum significantly improved neurological function and limb movement in rats with cerebral ischaemia during recovery and increased cerebral blood flow. l-Borneolum improved forelimb motor coordination more effectively than Borneolum and promoted transdifferentiation of astrocytes to GABAergic neurons in the striatal region. The expression of Wnt3a and Notch-1 was downregulated. The expression of vascular endothelial growth factor was not significantly changed. Borneolum improved forelimb sensitivity and alleviated cerebral infarction and brain atrophy more effectively than l-Borneolum, which promoted transdifferentiation of astrocytes into neurons and nestin expression and neurogenesis in the striatal zone. The expression of glycogen synthase kinase-3β and β-catenin was upregulated. l-Borneolum and Borneolum had no significant neuroprotective effect on the cortex and hippocampus. Conclusions: l-Borneolum and Borneolum exerted neuroprotective effects on cerebral ischaemia during recovery by promoting neurogenesis and blood circulation in the striatal and subventricular zones. Their mechanisms may be related to the Wnt3a and Notch-1 pathways.
Journal
Phytomedicine
Publish Year
2023
Experiment Subject
rat
Experiment Type
Animal Experiment
Phenotype Related
Cerebral Ischaemia; Cerebral Infarction; Acute Cerebral Ischaemia-reperfusion; Brain Atrophy
Paper Title Cn
Paper Title En
l-Borneol and d-Borneol promote transdifferentiation of astrocytes into neurons in rats by regulating Wnt/Notch pathway to exert neuroprotective effect during recovery from cerebral ischaemia
Bilingual Status
semi_complete