No abstract

The 2,3,5,6-tetramethylpyrazine (TMP) has been widely used in the treatment of ischemic stroke by Chinese doctors. Here, we report the effects of TMP on functional recovery and dendritic plasticity after ischemic stroke. A classical model of middle cerebral artery occlusion (MCAO) was established in this study. The rats were assigned into 3 groups: sham group (sham operated rats treated with saline), model group (MCAO rats treated with saline) and TMP group (MCAO rats treated with 20 mg/kg/d TMP). The neurological function test of animals was evaluated using the modified neurological severity score (mNSS) at 3 d, 7 d, and 14 d after MCAO. Animals were euthanized for immunohistochemical labeling to measure MAP-2 levels in the peri-infarct area. Golgi-Cox staining was performed to test effect of TMP on dendritic plasticity at 14 d after MCAO. TMP significantly improved neurological function at 7 d and 14 d after ischemia, increased MAP-2 level at 14 d after ischemia, and enhanced spine density of basilar dendrites. TMP failed to affect the spine density of apical dendrites and the total dendritic length. Data analyses indicate that there was significant negative correlation between mNSS and plasticity measured at 14 d after MCAO. Thus, enhanced dendritic plasticity contributes to TMP-elicited functional recovery after ischemic stroke.

Angelica sinensis has antioxidative and neuroprotective effects. In the present study, we aimed to determine the neuroprotective effect of polysaccharides isolated from Angelica sinensis. In a preliminary experiment, Angelica sinensis polysaccharides not only protected PC12 neuronal cells from H2O2-induced cytotoxicity, but also reduced apoptosis and intracellular reactive oxygen species levels, and increased the mitochondrial membrane potential induced by H2O2 treatment. In a rat model of local cerebral ischemia, we further demonstrated that Angelica sinensis polysaccharides enhanced the antioxidant activity in cerebral cortical neurons, increased the number of microvessels, and improved blood flow after ischemia. Our findings highlight the protective role of polysaccharides isolated from Angelica sinensis against nerve cell injury and impairment caused by oxidative stress.

Tetramethylpyrazine (TMP) has been widely used in ischemic stroke in China. The regulation of neuroplasticity may underlie the recovery of some neurological functions in ischemic stroke. Middle cerebral artery occlusion (MCAO) model was established in this study. Rats were divided into three groups: sham group, model group, and TMP group. The neurological function was evaluated using modified neurological severity score (mNSS). Following the neurological function test, expression of synaptophysin (SYP) and growth-associated protein 43 (GAP-43) were analyzed through immunohistochemistry at 3 d, 7 d, 14 d, and 28 d after MCAO. Finally, the synaptic structural plasticity was investigated using transmission electron microscopy (TEM). The TMP group showed better neurological function comparing to the model group. SYP levels increased gradually in ischemic penumbra (IP) in the model group and could be enhanced by TMP treatment at 7 d, 14 d, and 28 d, whereas GAP-43 levels increased from 3 d to 7 d and thereafter decreased gradually from 14 d to 28 d in the model group, which showed no significant improvement in the TMP group. The results of TEM showed a flatter synaptic interface, a thinner postsynaptic density (PSD), and a wider synaptic cleft in the model group, and the first two alterations could be ameliorated by TMP. Then, a Pearson’s correlation test revealed mNSS markedly correlated with SYP and synaptic ultrastructures. Taken together, TMP is capable of promoting functional outcome after ischemic stroke, and the mechanisms may be partially associated with regulation of neuroplasticity.

Chronic cerebral hypoperfusion (CCH) is closely related to vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). The neuroinflammation involving astrocytes is an important pathogenic mechanism. Along with the advancement of the concept and technology of astrocytic biology, the astrocytes have been increasingly regarded as the key contributors to neurological diseases. It is well known that physical exercise can improve cognitive function. As a safe and effective non-drug treatment, physical exercise has attracted continuous interests in neurological research. In this study, we explored the effects of physical exercise on the response of reactive astrocytes, and its role and mechanism in CCH-induced cognitive impairment. A rat CCH model was established by 2 vessel occlusion (2VO) and the wheel running exercise was used as the intervention. The cognitive function of rats was evaluated by morris water maze and novel object recognition test. The phenotypic polarization and the primary cilia expression of astrocytes were detected by immunofluorescence staining. The activation of MAPKs cascades, including ERK, JNK, and P38 signaling pathways, were detected by western blot. The results showed that physical exercise improved cognitive function of rats 2 months after 2VO, reduced the number of C3/GFAP-positive neurotoxic astrocytes, promoted the expression of S100A10/GFAP-positive neuroprotective astrocytes, and enhanced primary ciliogenesis. Additionally, physical exercise also alleviated the phosphorylation of ERK and JNK proteins induced by CCH. These results indicate that physical exercise can improve the cognitive function of rats with CCH possible by promoting primary ciliogenesis and neuroprotective function of astrocytes. The MAPKs signaling cascade, especially ERK and JNK signaling pathways may be involved in this process.