Protective efficacy of a single salvianolic acid A treatment on photothrombosis-induced sustained spatial memory impairments

Abstract

With respect to the high burden of ischemic stroke and the absence of pharmacological treatment for promoting rehabilitation, promising candidates with specific effects on long-term functional recovery are highly desired. Candidates need reasonable experimental paradigms to evaluate the long-term functional outcome focused on ischemia-induced sensorimotor and memory deficits. “Danshen”, a traditional Chinese herb, has long been used to treat coronary and cerebral vascular diseases as well as dementia. Salvianolic acid A (SAA), one of the major active ingredients of Danshen, was demonstrated to be effective in protecting against cerebral ischemic injury. Here, employing an experimental stroke model induced by photothrombosis in the unilateral frontal cortex of rats, we investigated whether SAA has long-term protective effects on ischemia-induced sensorimotor and memory deficits in our behavioral tests. The results indicated that a single SAA treatment improved the cortical ischemia-induced sensorimotor deficits during 15 days’ cylinder test period, and alleviated ischemia-induced sustained spatial memory impairments during the 2 months’ dependent Morris Water Maze (MWM) tests. In addition, either ischemic injury or SAA treatment did not show any changes compared with sham group in other behavioral tests including rotarod tests, swimming speed in MWM tests, open field tests, elevated plus maze tests, treadmill tests and forced swimming tests. The results reveal that the cognitive deficits are not the results of animal’s anxiety or confounding motor impairments. Overall, the present paradigm appears suitable for the preclinical evaluation of the long-term effects of pharmacological treatments on ischemic stroke. Meanwhile, SAA might have therapeutic potential for the treatment of memory deficits associated with ischemic stroke.

Developing of Focal Ischemia in the Hippocampus or the Amygdala Reveals a Regional Compensation Rule for Fear Memory Acquisition

“…Third, the damage induced by ischemia shows a developing process that it enables us to test the impact of different levels of damage on contextual fear memory, which is ignored in the previous ( Felberg et al, 2000 ). This model could be also applied to study the mechanism of ischemia induced amnesia and the efficacy of neuroprotective drugs ( Esiri et al, 1999 ; Yu et al, 2015 ; Jiao et al, 2017 ).…”

“…However, for other purposes, the researchers need to adjust the related parameters including the laser power and the location of the optical-fiber tips to reduce the potential damage at adjacent areas. Meanwhile, it was worthwhile to note that the Nissl staining or immunofluorescence is much greater in the high-magnification image than TTC staining ( Jiao et al, 2017 ). We still applied the TTC staining for most experiments because the Nissl staining was not sensitive at the early stage of ischemia, and the tissues were two fragile during 50-μm slice preparation especially for the animals with 24-h injury at the amygdala, and the TTC staining was the good selection for the brain slices that already were applied to the electrophysiological recording.…”

Research progress of natural products for the treatment of ischemic stroke

“…SAA can significantly reduce the cerebral infarct area and brain water content of tMCAO rats, reduce neurological deficits and pathological changes, and enhance the anti-inflammatory and antioxidant capacities of tMCAO rats [89]. SAA was shown to improve the sensorimotor and persistent memory impairments caused by focal ischemia in the unilateral frontal cortex of rats, suggesting that SAA has therapeutic potential in the treatment of IS-related memory impairment [90]. In addition, SAA can inhibit the production of ONOO-, up-regulate the phosphorylation levels of protein kinase B (AKT), forkhead transcription factor (FKHR) and extracellular signal-regulated kinase (ERK), increase glucose metabolism after cerebral ischemia, reduce neurological deficits, and protect the brain from ischemia/reperfusion injury [91].…”

Effects of Various Cleaning Agents on the Performance of Mice in Behavioral Assays of Anxiety

“…16 Finally, many studies that make no mention of cleaning whatsoever. 12,14,17,22 The goal of this study was to determine whether the cleaning of EPM apparatus affects animal performance, because few data in this field are available. One study in mice showed decreased anxiety and neophobia in a light:dark test when tested on a soiled apparatus as compared with a clean device.…”