The temporal dynamic of bradykinin type 2 receptor effects reveals its neuroprotective role in the chronic phase of cerebral and retinal ischemic injury.

The activation of the bradykinin type 2 receptor is intricately involved in acute post-ischemic inflammatory responses. However, its precise role in different stages of ischemic injury, especially in the chronic phase, remains unclear. Following simultaneous cerebral and retinal ischemia, bradykinin type 2 receptor knockout mice and their controls were longitudinally monitored for 35 days via magnetic resonance imaging, fundus photography, fluorescein angiography, behavioral assessments, vascular permeability measurements, and immunohistochemistry, as well as glycemic status assessments. Without impacting the lesion size, bradykinin type 2 receptor deficiency reduced acute cerebral vascular permeability preventing the loss of pericytes and tight junctions. In the chronic phase of ischemia, however, it resulted in increased astrogliosis and cortical neuronal loss, as well as higher functional deficits. The retinal findings demonstrated a similar pattern. Bradykinin type 2 receptor deficiency delayed, but exacerbated the development of retinal necrosis, increased subacute vascular permeability, and promoted retinal ganglion cell loss in the chronic phase of ischemia. This investigation sheds light on the temporal dynamic of bradykinin type 2 receptor effects in ischemia, pointing to a therapeutic potential in the subacute and chronic phases of ischemic injury.

Innovative statistical approaches: the use of neural networks reduces the sample size in the splenectomy-MCAO mouse model.

AIM: To compare the effectiveness of artificial neural network (ANN) and traditional statistical analysis on identical data sets within the splenectomy-middle carotid artery occlusion (MCAO) mouse model. METHODS: Mice were divided into the splenectomized (SPLX) and sham-operated (SPLX-sham) group. A splenectomy was conducted 14 days before middle carotid artery occlusion (MCAO). Magnetic resonance imaging (MRI), bioluminescent imaging, neurological scoring (NS), and histological analysis, were conducted at two, four, seven, and 28 days after MCAO. Frequentist statistical analyses and ANN analysis employing a multi-layer perceptron architecture were performed to assess the probability of discriminating between SPLX and SPLX-sham mice. RESULTS: Repeated measures ANOVA showed no significant differences in body weight (F (5, 45)=0.696, P=0.629), NS (F (2.024, 18.218)=1.032, P=0.377) and brain infarct size on MRI between the SPLX and SPLX-sham groups post-MCAO (F (2, 24)=0.267, P=0.768). ANN analysis was employed to predict SPLX and SPL-sham classes. The highest accuracy in predicting SPLX class was observed when the model was trained on a data set containing all variables (0.7736±0.0234). For SPL-sham class, the highest accuracy was achieved when it was trained on a data set excluding the variable combination MR contralateral/animal mass/NS (0.9284±0.0366). CONCLUSION: This study validated the neuroprotective impact of splenectomy in an MCAO model using ANN for data analysis with a reduced animal sample size, demonstrating the potential for leveraging advanced statistical methods to minimize sample sizes in experimental biomedical research.