Background Hypoxic-Ischemic Encephalopathy (HIE) occurs when an infant's brain does not receive adequate blood and oxygen supply, resulting in ischemic and hypoxic brain damage during delivery. Currently, supportive care and hypothermia have been the standard treatment for HIE. However, there are still a 20% mortality and most of the survivors are associated with significant neurodevelopmental disability. HIE animal model was first established by Vannucci et al., in 1981, and has been used extensively to explore the mechanisms of brain damage and its potential treatment. The Vannucci model involves the unilateral common carotid artery occlusion followed by 90 min hypoxia (8% oxygen). The purpose of this study is to define and validate a modified HIE model which mimics closely that of the human neonatal HIE. Method The classic Vannucci HIE model occludes one common carotid artery followed by 90 min hypoxia. In the new model, common carotid arteries were occluded bilaterally followed by breathing 8% oxygen in a hypoxic chamber for 90, 60 and 30 min, followed by the release of the common carotid artery ligatures, mimicking a reperfusion. Result We studied 110 neonatal rats in detail, following the modified in comparison with the classical Vannucci models. The classical Vannucci model has a consistent surgical mortality of 18% and the new modified models have a 20%–46%. While mortality depended on the duration of hypoxia, fifty-two animals survived for behavioral assessments and standard histology. The modified HIE model with 60 min of transient carotid occlusion is associated with a moderate brain damage, and has a 30% surgical mortality. This modified experimental model is regarded closer to the human situation than the classical Vannucci model.

Subarachnoid hemorrhage (SAH) is a subtype of stroke with disastrous outcomes of high disability and mortality. A variety of endeavors have been developed to explore a SAH animal model for investigation of the disease. Among these models, the endovascular perforation SAH model was considered to be the most simulative to the clinical human SAH because it reproduces several pathophysiology procedures and presents some of the most important post-hemorrhage features. An applicable SAH animal model should have the characteristics of low mortality rate, limited surgical manipulation, and adaptation to many species, which permits reproducibility and standardization. An intensive discussion of how to improve the techniques and refine the procedure has taken place in the last decade. This report describes our experiences with a murine model of SAH. We aim to standardize and optimize the procedures to establish a relatively stable animal model for SAH research.

BackgroundHypoxic-ischemic encephalopathy (HIE) occurs when an infant’s brain has not received adequate oxygen and blood supply, resulting in ischemic and hypoxic damage. Currently, supportive care and hypothermia therapy have been the standard treatment for HIE. However, there are still over 20% of treated infants died and 19–30% survived with significant disability. HIE animal model was first established by Rice et al., involving the ligation of one common carotid artery followed by hypoxia. In this study, we investigated human umbilical cord blood (HUCB) and its two components mononuclear cell (MNC) and red cell fraction (RCF) in both short and long term study using a modified HIE rat model.MethodsIn this modified HIE model, both common carotid arteries were occluded, breathing 8% oxygen in a hypoxic chamber for 60-min, followed by the release of the common carotid arteries ligature, mimicking reperfusion injury. For cell therapeutic study, cells were intravenously injected to HIE rat pups, and both behavioral and histological changes were assessed at selected time points.ResultStatistically significant behavioral improvements were demonstrated on Day 7 and 1 month between saline treated HIE rats and UCB/MNC treated rats. However, at 3 months, the therapeutic improvements were only showed between saline treated HIE animals and MNC treated HIE rats. For histological analysis 1 month after cell injection, the number of functional neurons were statistically increased between saline treated HIE and UCB/MNC/RCF treated HIE rats. At 3 months, the significant increase in functional neurons was only present in MNC treated HIE rats.ConclusionWe have used a bilateral temporary occlusion of 60 min, a moderately brain damaged model, for cell therapeutic studies. HUCB mononuclear cell (MNC) therapy showed benefits in neonatal HIE rats in both short and long term behavioral and histological assessments.

Gait analysis has been widely used to examine the behavioral presentation of numerous neurological disorders. Thorough murine model evaluation of the subarachnoid hemorrhage (SAH)‐associated gait deficits is missing. This study measures gait deficits using a clinically relevant murine model of SAH to examine associations between gait variability and SAH‐associated gene expressions. A total of 159 dynamic and static gait parameters from the endovascular perforation murine model for simulating clinical human SAH were determined using the CatWalk system. Eighty gait parameters and the mRNA expression levels of 35 of the 88 SAH‐associated genes were differentially regulated in the diseased models. Totals of 42 and 38 gait parameters correlated with the 35 SAH‐associated genes positively and negatively with Pearson's correlation coefficients of >0.7 and <−0.7, respectively. p‐SP1453 expression in the motor cortex in SAH animal models displays a significant correlation with a subset of gait parameters associated with muscular strength and coordination of limb movements. Our data highlights a strong correlation between gait variability and SAH‐associated gene expression. p‐SP1453 expression could act as a biomarker to monitor SAH pathological development and a therapeutic target for SAH.