Background: Chronic cerebral hypoperfusion is a common pathophysiological state in
various cerebrovascular diseases. Anisodine has been reported to exert neuroprotective effects in cerebral
ischemia/reperfusion (I/R) animal model. However, it is unclear whether anisodine hydrobromide,
the hydrobromide format of anisodine, one of the tropic alkanes alkaloids, exhibits the same neuroprotective
effect on chronic cerebral hypoperfusion(CCH) rats. Herein, we tried to unravel these issues.
Methods: CCH model in adult male Sprague-Dawley rats was established by permanent ligation of the
bilateral common carotid arteries [two-vessel occlusion (2-VO)] surgery. Rats were randomly divided
into six groups: sham, 2-VO, 2-VO + Butyl phthalide and sodium chloride injection (NBP, as positive
control group), 2-VO + anisodine hydrobromide (AH)1.2mg/kg, 2-VO +AH0.6mg/kg, 2-VO
+AH0.3mg/kg. Cognitive behavior was examined by Morris Water Maze Test. Neuronal survival and
apoptosis were evaluated by Nissl staining and Terminal-deoxynucleoitidyl transferase mediated nick
end labeling (TUNEL staining). The relative monoamine neurotransmitter (5-hydroxytryptamine
(5-HT), norepinephrine (NA)), the content of Ach, the activity of acetylcholin esterase (AchE) were
measured in cholinergic system, and the protein expressions of Bcl-2, Bax, p-Akt and p-GSK-3βwere
detected by Western blot assay.
Results: The results showed that there is significant memory impairment and a remarkable neuron necrosis
and apoptosis, along with the dysfunction of the neurotransmitter systems and central cholinergic
system in CCH rats. AH treatment could significantly improve cognitive deficits, while reducing
neuron necrosis and apoptosis, apart from increasing the content of 5-HT and decreasing the activity
of AchE markedly. Further study revealed that AH could promote the protein expression of Bcl-2,
phosphorylation of Akt and GSK-3β, and downregulate the protein of Bax.
Conclusion: AH was demonstrated to ameliorate memory deficits by revising the imbalance of the
monoamine neurotransmitter and cholinergic dysfunction. Moreover, AH can attenuate neuronal cell
death and apoptosis by activating the Akt/GSK-3βsignaling pathway.