Aerobic exercise improves motor dysfunction in Parkinson's model mice via differential regulation of striatal medium spiny neuron.

The striatum plays a crucial role in providing input to the basal ganglia circuit and is implicated in the pathological process of Parkinson's disease (PD). Disruption of the dynamic equilibrium in the basal ganglia loop can be attributed to the abnormal functioning of the medium spiny neurons (MSNs) within the striatum, potentially acting as a trigger for PD. Exercise has been shown to mitigate striatal neuronal dysfunction through neuroprotective and neurorestorative effects and to improve behavioral deficits in PD model mice. In addition, this effect is offset by the activation of MSNs expressing dopamine D2 receptors (D2-MSNs). In the current study, we investigated the underlying neurobiological mechanisms of this effect. Our findings indicated that exercise reduces the power spectral density of the beta-band in the striatum and decreases the overall firing frequency of MSNs, particularly in the case of striatal D2-MSNs. These observations were consistent with the results of molecular biology experiments, which revealed that aerobic training specifically enhanced the expression of striatal dopamine D2 receptors (D2R). Taken together, our results suggest that aerobic training aimed at upregulating striatal D2R expression to inhibit the functional activity of D2-MSNs represents a potential therapeutic strategy for the amelioration of motor dysfunction in PD.

Early intervention of carbon dioxide fractional laser in hypertrophic scar through TGFß-1/ Smad3 signaling pathway.

Hypertrophic scars are usually the result of surgical trauma or burn,and more common in individuals with a darker skin color. They appear as red and raised lesions around the wound that continually expand over a period of weeks or months, causing itching, pain, burning sensation and discomfort. Severe scarring affects interpersonal and social relationships, and decreases the quality of life of the patients.The aim of this study was to evaluate the effect of carbon dioxide fractional laser as an early intervention against hypertrophic scars using a rabbit ear scar model, and explore the role of the TGFß-1/ Smad3 signaling pathway in scar hyperplasia. Four wounds were made into each ear of rabbits, and divided into the untreated control and three laser-treatment groups. The experimental groups received laser intervention once, twice and thrice respectively. laser treatment significantly inhibited the formation of hypertrophic scars, and maximum benefits were seen in the wounds that received three laser treatments. Immunohistochemical staining showed that the in situ expression of TGFß-1 and Smad3 in the scars decreased by varying degrees after laser intervention, and was most obvious after three laser interventions. Furthermore, the expression levels were the lowest at the end of 6 months after modeling. Therefore, we can assume that early intervention with carbon dioxide fractional laser can prevent formation of hypertrophic scars by regulating the TGF-ß1/Smad3 pathway.

Concentration-Dependent Inhibition of Hypertrophic Scar Formation by Botulinum Toxin Type A in a Rabbit Ear Model.

BACKGROUND: Hypertrophic scar (HS), as a disappointing result of wound healing, adversely affects the patient, both physically and psychologically. Botulinum toxin type A (BTXA) has been revealed to prevent and improve HS. We conducted this study to assess the effect of different BTXA concentrations on inhibiting HS in a rabbit ear model. METHODS: Eight healthy New Zealand long-eared rabbits were included in the experiment for modeling. Four wounds of 1 cm in diameter were created on both ears, which separately received an injection of a given BTXA concentration immediately after surgery. On postoperative days 40, scar tissue was obtained and subjected to hematoxylin and eosin (HE) staining for the hypertrophic index (HI) and immunohistochemical staining for CD31, Ki67, and transforming growth factor-beta 1 (TGF-ß1) expression. The HI was assessed for scar proliferation, and CD31 and Ki67 expression were used to assess the effect of BTXA on angiogenesis and fibroblast proliferation, respectively. RESULTS: All rabbits healed well without infection or mortality. From the HE staining, the HI showed a significant decrease with increasing BTXA concentration (p < 0.05). BTXA also inhibited angiogenesis and TGF-ß1 expression in a concentration-dependent manner, with significant differences between the groups (p < 0.05). BTXA inhibited fibroblast proliferation with increasing BTXA concentration. However, there was no significant difference between the 0.5 U/0.1 ml and 0 U/0.1 ml groups (p > 0.05). CONCLUSION: Immediate postoperative BTXA injection inhibited angiogenesis, fibroblast proliferation, and TGF-ß1 expression in a concentration-dependent manner, thus suppressing HS formation in rabbit ears. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/journal/00266 .

Early intervention of fractional carbon dioxide laser on fresh traumatic scar.

To determine the combined therapeutic effect of fractional carbon dioxide laser and silicone gel on fresh traumatic scars using a rabbit ear hypertrophic scar (EHS) model, as well as on human subjects. The rabbit EHS model was established by punching four circular wounds in each ear and respectively treated with carbon dioxide laser, silicone gel, and the combination of both, while one wound was left untreated. In addition, a validation group of five rabbits was also included wherein the wounds were treated with triamcinolone, IFN-α, and normal saline, with one untreated control. The gross hyperplasic changes and the histological features were analyzed, and the scar elevation index (SEI) was calculated for each treatment group. In the rabbit model, the untreated control wounds showed hypertrophic growth, whereas triamcinolone or IFN-α showed an inhibitory effect, similar to that on hypertrophic scars in humans, thereby proving the feasibility of our animal model. The SEI peaked 2 months after treatment and was respectively 2.28 ± 0.56, 1.85 ± 0.33, 1.91 ± 0.34, and 1.45 ± 0.22 in the untreated control, and the silicone, laser, and combined treatment groups, clearly indicating a significant therapeutic effect of the combined treatment modality (p < 0.01). The fibroblast and microvascular counts also showed similar trends in each group. Early application of fractional carbon dioxide laser can prevent hypertrophic scars; the combined use of laser and silicone gel was more effective with less recovery time, thereby worthy of clinical promotion.