Abstract:
Background Although NBO therapy has been demonstrated to exert significant neuroprotective effects in both animal and clinical trials, research into the combination of NBO with thrombectomy remains in its early stages. The efficacy of combining oxygen therapy with hypothermia treatment has thus far been studied in only a handful of animal experiments 149. The combination of NBO and selective brain hypothermia may represent an ideal early stroke treatment method for preserving the ischaemic penumbra. Our hypothesis is that the neuroprotective effects of NBO are verifiable and can be enhanced through combined application of NBO and ICCI hypothermia.
Methods Upon establishing a 60-min MCAO rat model, rats were randomly allocated into three groups (24h group: n=4/group; 2 weeks group: n=12/group): CTR (no treatment), NBO (mask inhalation of 100% oxygen) and CB (combination treatment of NBO and ICCI ， 0-1 ℃ 0.9% saline infusion via ICA). The primary outcome parameter chosen for this study was the volume of cerebral infarction detected using T2-MRI at 14 days. We selected the infarct volume and cerebral oedema on the ADC map 24 h after MCAO as secondary outcome parameters. Using conventional H&E staining to examine the extent of damage. Subsequently, some staining methods were employed based on the duration post-stroke: 1) The 24-hour group received H&E staining, along with GFAP, Hypoxyprobe and NeuN; 2) The 14-day group was subjected to NeuN, GFAP, CD31, and Iba1. Additionally, neuroscore tests and blood gas analysis were conducted.
Results Analysis of the experimental results revealed that, compared with that in control group, the striatal infarct volume in NBO group was significantly reduced according to the striatal infarct volume obtained from T2-MRI at 14 days. Additionally, for the cerebral cortical infarct volume measured by the apparent diffusion coefficient (ADC) at 24 h, the cortical infarct volume in the combined treatment group was significantly reduced compared to that in NBO group. Moverover, in the hypoxyprobe analysis, the use of NBO, ICCl, or a combination of both treatments significantly reduced hypoxia in the cortex following stroke. Additionally, significant differences in post treatment pH, PCO2 and PO2 were observed among the three groups of rats.
Discussion We confirmed the potent neuroprotective effect of NBO, and showed augmentation of effectiveness when combined with ICCI. Thus, early combination treatment may potentially be useful in ischaemic stroke to further reduce resulting infarct volumes. Nevertheless, the observed respiratory acidosis observed during combined use of ICCI and NBO, as well as the trend towards aggravated cerebral oedema, remains concerning and warrants caution. Future studies should incorporate mechanically ventilation for enabling the control of blood gases.
Intracarotid cold infusion