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

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.

Age-related CCL12 Aggravates Intracerebral Hemorrhage-induced Brain Injury via Recruitment of Macrophages and T Lymphocytes

“…The results showed that the NDS, mortality rate, BWC of perihematomal brain tissues and levels of inflammatory cytokines, such as IL-6, IL-10 and TNF-α, were lower in old mice than in young mice after ICH ( Supplementary Fig. 1), which was consistent with our previous research [13].…”

“…In the current study, we elucidated the roles and mechanisms of CCL12 in aggravating age-related brain injury after ICH. As reported previously, old mice have worse outcomes than young mice after ICH [13]. Furthermore, we observed that the brain and plasma CCL12 levels were markedly upregulated in old mice compared with young mice regardless of ICH, and circulating CCL12 was demonstrated to enter the brain, where it initiated proinflammatory responses.…”

“…Male mice with similar weights and sizes were first housed together for 2-3 weeks before surgery, and the procedures were performed as described previously [13]. Wild-type (WT) mice were used as parabiotic donors of CCL12 to CCL12 -/mice.…”

“…Following our previously described method [13], brain tissues were removed from euthanized mice and fixed in 4% paraformaldehyde. Next, the samples were dehydrated in a series of graded ethanol solutions and then embedded in paraffin for sectioning with a rotary microtome into 4.5-μm-thick slices.…”

Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage

“…The ICH model was conducted according to our previously developed method (Yuan et al, 2019). Briefly, mice were immobilized on the stereotaxic apparatus (RWD Life Science Co, Shenzhen, China) after being anesthetized with 3% isoflurane for induction and 1.5% for maintenance.…”