Temporal and age-dependent effects of haptoglobin deletion on intracerebral hemorrhage-induced brain damage and neurobehavioral outcomes

Aims We have recently created an age-dependent hypertensive-mono-arthritic animal model from the stroke-resistant spontaneously hypertensive rat to model populations with autoimmune disease who are hypertensive and are prone to stroke. The model exhibits signs of hemorrhagic stroke (HS) subsequent to chronic inflammation and hypertension. HS is also associated with the inability of middle cerebral arteries to undergo pressure dependent constriction (PDC). We investigated alterations in the cerebrovasculature of our hypertensive mono-arthritic animals that develop stroke. Main Methods Animals were fed either a high salt diet (HSD) (4% NaCl) or Purina chow (0.58% NaCl) from weaning. Complete Freund’s Adjuvant (CFA) was injected into the left hind paw at 21–28 weeks; controls received saline and histological and functional studies were performed. Results Brain damage was more prominent with the high salt, with inflammation exacerbating the damage. High salt alone significantly decreased middle cerebral artery’s (MCA’s) ability to undergo PDC. Inflammation significantly decreased the ability of cerebrovasculature to respond to pressure step in the regular salt diet. The responses to vasoactive peptides were also significantly attenuated in both inflamed groups regardless of diet. Conclusion Induction of chronic systemic inflammation increases brain damage, and affect the MCA’s vasogenic function, decreasing its ability to respond to intraluminal pressure. HSD further exacerbates organ damage associated with chronic inflammation, further compromising cerebrovascular function, and likely increasing the incidence of intracerebral hemorrhage and injury.

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Safety and efficacy of normobaric oxygenation on rescuing acute intracerebral hemorrhage-mediated brain damage—a protocol of randomized controlled trial

Trials ◽

10.1186/s13063-021-05048-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhiying Chen ◽

Jiayue Ding ◽

Xiaoqin Wu ◽

Bing Bao ◽

Xianming Cao ◽

...

Keyword(s):

Computed Tomography ◽

Intracerebral Hemorrhage ◽

Brain Damage ◽

Controlled Trial ◽

Low Flow ◽

Control Group ◽

Oxygen Control ◽

Safety And Efficacy ◽

High Flow Oxygen ◽

Secondary Endpoints

Abstract Background All of the existing medication and surgical therapies currently cannot completely inhibit intracerebral hemorrhage (ICH)-mediated brain damage, resulting in disability in different degrees in the involved patients. Normobaric oxygenation (NBO) was reported attenuating ischemic brain injury. Herein, we aimed to explore the safety and efficacy of NBO on rescuing the damaged brain tissues secondary to acute ICH, especially those in the perihematoma area being threatened by ischemia and hypoxia. Methods A total of 150 patients confirmed as acute spontaneous ICH by computed tomography (CT) within 6 h after symptoms onset, will enroll in this study after signing the informed consent, and enter into the NBO group or control group randomly according to a random number. In the NBO group, patients will inhale high-flow oxygen (8 L/min, 1 h each time for 6 cycles daily) and intake low-flow oxygen (2 L/min) in intermittent periods by mask for a total of 7 days. While in the control group, patients will breathe in only low-flow oxygen (2 L/min) by mask for 7 consecutive days. Computed tomography and perfusion (CT/CTP) will be used to evaluate cerebral perfusion status and brain edema. CT and CTP maps in the two groups at baseline and day 7 and 14 after NBO or low-flow oxygen control will be compared. The primary endpoint is mRS at both Day14 post-ICH and the end of the 3rd month follow-up. The secondary endpoints include NIHSS and plasma biomarkers at baseline and Day-1, 7, and 14 after treatment, as well as the NIHSS at the end of the 3rd month post-ICH and the incidence of bleeding recurrence and the mortalities within 3 months post-ICH. Discussion This study will provide preliminary clinical evidence about the safety and efficacy of NBO on correcting acute ICH and explore some mechanisms accordingly, to offer reference for larger clinical trials in the future. Trial registration ClinicalTrials.gov NCT04144868. Retrospectively registered on October 29, 2019.

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Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage

Bioscience Reports ◽

10.1042/bsr20190537 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 4

Author(s):

Jun-Jie Yuan ◽

Qin Zhang ◽

Chang-Xiong Gong ◽

Fa-Xiang Wang ◽

Jia-Cheng Huang ◽

...

Keyword(s):

Brain Injury ◽

Intracerebral Hemorrhage ◽

Brain Damage ◽

Mrna Level ◽

Acute Brain Injury ◽

Aging Brain ◽

Neural Cells ◽

Neuroprotective Effects ◽

The Brain ◽

Brain Tissues

Abstract Aging has been shown to contribute to both the declined biofunctions of aging brain and aggravation of acute brain damage, and the former could be reversed by young plasma. These results suggest that young plasma treatment may also reduce the acute brain damage induced by intracerebral hemorrhage (ICH). In the present study, we first found that the administration of young plasma significantly reduced the mortality and neurological deficit score in aging ICH rodents, which might be due to the decreased brain water content, damaged neural cells, and increased survival neurons around the perihematomal brain tissues. Then, proteomics analysis was used to screen out the potential neuroprotective circulating factors and the results showed that many factors were changed in health human plasma among young, adult, and old population. Among these significantly changed factors, the plasma insulin-like growth factor 1 (IGF-1) level was significantly decreased with age, which was further confirmed both in human and rats detected by ELISA. Additionally, the brain IGF-1 protein level in aging ICH rats was markedly decreased when compared with young rats. Interestingly, the relative decreased brain IGF-1 level was reversed by the treatment of young plasma in aging ICH rats, while the mRNA level was non-significantly changed. Furthermore, the IGF-1 administration significantly ameliorated the acute brain injury in aging ICH rats. These results indicated that young circulating factors, like IGF-1, may enter brain tissues to exert neuroprotective effects, and young plasma may be considered as a novel therapeutic approach for the clinical treatment of aging-related acute brain injury.

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